Riociguat

Cancer Res[Jour] AND 85[volume] AND 1 [issue] 癌症研究 85卷 1期 https://aacrjournals.org/cancerres/issue/ In the Spotlight（焦点） 1 Persistence and/or Senescence: Not So Lasting at Last? 坚持和/或衰老：终于不那么持久了？ Clemens A. Schmitt Cancer Res (2025) 85 (1): 7–9. 2 Peritumoral Venous Vessels: Autobahn and Portal for T Cells to Melanoma Brain Metastasis 瘤周静脉血管：T细胞通向黑色素瘤脑转移的高速公路和门户 Benjamin Izar; Minah Kim Cancer Res (2025) 85 (1): 10–11. 3 Tumor Heterogeneity and Cooperating Cancer Hallmarks Driven by Divergent EMT Programs 不同EMT程序驱动的肿瘤异质性与癌症协同效应特征 Phoebe Carter; Yibin Kang Cancer Res (2025) 85 (1): 12–14. Resource Report（资源报告） 4 Distant Metastases of Breast Cancer Resemble Primary Tumors in Cancer Cell Composition but Differ in Immune Cell Phenotypes 乳腺癌远端转移与原发肿瘤癌细胞的组成相似但免疫细胞的表型不同 Laura Kuett; Alina Bollhagen; Sandra Tietscher; Bettina Sobottka; Nils Eling; Zsuzsanna Varga; Holger Moch; Natalie de Souza; Bernd Bodenmiller Cancer Res (2025) 85 (1): 15–31. Cancer Biology（癌症生物学） 5 H4K20me3-Mediated Repression of Inflammatory Genes Is a Characteristic and Targetable Vulnerability of Persister Cancer Cells H4K20me3-介导的炎症基因抑制是持久性癌症细胞的特征和脆弱性靶标 Valentina Ramponi; Laia Richart; Marta Kovatcheva; Camille Stephan-Otto Attolini; Jordi Capellades; Alice E. Lord; Oscar Yanes; Gabriella Ficz; Manuel Serrano Cancer Res (2025) 85 (1): 32–51. 6 LSD1 and CoREST2 Potentiate STAT3 Activity to Promote Enteroendocrine Cell Differentiation in Mucinous Colorectal Cancer LSD1和CoREST2增强STAT3活性促进粘液性大肠癌肠内分泌细胞分化 Christopher A. Ladaika; Ahmed H. Ghobashi; William C. Boulton; Samuel A. Miller; Heather M. O’Hagan Cancer Res (2025) 85 (1): 52–68. 7 HIF1α Counteracts TGFβ1-Driven TSP1 Expression in Endothelial Cells to Stimulate Angiogenesis in the Hypoxic Tumor Microenvironment HIF1α拮抗TGFβ1驱动的内皮细胞TSP1表达，以刺激缺氧肿瘤微环境中的血管生成 Yu-Wei Luo; Yang Fang; Hui-Xian Zeng; Yu-Chen Ji; Meng-Zhi Wu; Hui Li; Jie-Ying Chen; Li-Min Zheng; Jian-Hong Fang; Shi-Mei Zhuang Cancer Res (2025) 85 (1): 69–83. Cancer Metabolism and Molecular Mechanisms（癌症代谢与分子机制） 8 TCTN1 Induces Fatty Acid Oxidation to Promote Melanoma Metastasis TCTN1诱导脂肪酸氧化促进黑色素瘤转移 Yinlam Li; Ren Ming; Tianyi Zhang; Zixu Gao; Lu Wang; Yang Yang; Kangjie Shen; Chenlu Wei; Yu Zhu; Jianrui Li; Shaoluan Zheng; Zucheng Luo; Yiteng Ding; Jiangying Xuan; Qianrong Hu; Yanwen Yang; Jianying Gu; Chuanyuan Wei Cancer Res (2025) 85 (1): 84–100. Therapeutic Development and Chemical Biology（治疗进展与生物化学） 9 Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR–ABL–Positive Leukemia SOS1的靶向降解在KRAS突变肿瘤和BCR-ABL阳性白血病中显示出强大的抗癌活性且可抗耐药 Ziwei Luo; Chencen Lin; Chuwei Yu; Changxian Yuan; Wenyong Wu; Xiaowei Xu; Renhong Sun; Yan Jia; Yafang Wang; Jie Shen; Dingyan Wang; Sinan Wang; Hualiang Jiang; Biao Jiang; Xiaobao Yang; Chengying Xie Cancer Res (2025) 85 (1): 101–117. Translational Cancer Biology（癌症转化生物学） 10 SOS1 Inhibition Enhances the Efficacy of KRASG12C Inhibitors and Delays Resistance in Lung Adenocarcinoma SOS1抑制增强KRASG12C抑制剂的疗效并延缓肺腺癌的耐药性 Brianna R. Daley; Nancy E. Sealover; Bridget A. Finniff; Jacob M. Hughes; Erin Sheffels; Daniel Gerlach; Marco H. Hofmann; Kaja Kostyrko; Joseph P. LaMorte; Amanda J. Linke; Zaria Beckley; Andrew M. Frank; Robert E. Lewis; Matthew D. Wilkerson; Clifton L. Dalgard; Robert L. Kortum Cancer Res (2025) 85 (1): 118–133. 11 Stimulating Soluble Guanylyl Cyclase with the Clinical Agonist Riociguat Restrains the Development and Progression of Castration-Resistant Prostate Cancer 临床激动剂利奥雪卡刺激可溶性鸟苷酸环化酶抑制去势抵抗的前列腺癌的发生发展 Ling Zhang; Clara I. Troccoli; Beatriz Mateo-Victoriano; Laura Misiara Lincheta; Erin Jackson; Ping Shu; Trisha Plastini; Wensi Tao; Deukwoo Kwon; Xi Steven Chen; Janaki Sharma; Merce Jorda; Surinder Kumar; David B. Lombard; James L. Gulley; Marijo Bilusic; Albert C. Lockhart; Annie Beuve; Priyamvada Rai Cancer Res (2025) 85 (1): 134–153. 12 Replication Stress Is an Actionable Genetic Vulnerability in Desmoplastic Small Round Cell Tumors 复制应激是促纤维增生性小圆细胞肿瘤中一种可操作的遗传易感性 Asuka Kawai-Kawachi; Madison M. Lenormand; Clémence Astier; Noé Herbel; Meritxell B. Cutrona; Carine Ngo; Marlène Garrido; Thomas Eychenne; Nicolas Dorvault; Laetitia Bordelet; Feifei Song; Ryme Bouyakoub; Anastasia Loktev; Antonio Romo-Morales; Clémence Henon; Léo Colmet-Daage; Julien Vibert; Marjorie Drac; Rachel Brough; Etienne Schwob; Oliviano Martella; Guillaume Pinna; Janet M. Shipley; Sibylle Mittnacht; Astrid Zimmermann; Aditi Gulati; Olivier Mir; Axel Le Cesne; Matthieu Faron; Charles Honoré; Christopher J. Lord; Roman M. Chabanon; Sophie Postel-Vinay Cancer Res (2025) 85 (1): 154–170. Computational Cancer Biology and Technology（计算癌症生物学与技术） 13 SpatialDeX Is a Reference-Free Method for Cell-Type Deconvolution of Spatial Transcriptomics Data in Solid Tumors SpatialDeX是实体瘤中空间转录组学数据细胞类型反卷积的无参考方法 Xinyi Liu; Gongyu Tang; Yuhao Chen; Yuanxiang Li; Hua Li; Xiaowei Wang Cancer Res (2025) 85 (1): 171–182. Acknowledgment to Reviewers（鸣谢编委会） 14 Acknowledgment to Reviewers 鸣谢编委会 Cancer Res (2025) 85 (1): 183–188. Cancer Res[Jour] AND 85[volume] AND 2[issue] 癌症研究85卷 2期 https://aacrjournals.org/cancerres/issue/ In the Spotlight（焦点） 1 Transcription Factor Fingerprint Provides Clues for Brain Tumor Cell of Origin 转录因子指纹图谱为脑肿瘤细胞起源提供线索 Brent A. Orr Cancer Res (2025) 85 (2): 195–196. 2 Midkine at the Crossroads of Aging and Cancer 处于衰老与癌症十字路口的Midkine（一种与肝素结合的生长因子） Huiru Bai; Shang Cai Cancer Res (2025) 85 (2): 197–199. 3 Stayin' Alive: Targeting Chromatin Regulators of Clonal Hematopoiesis Promotes CD8 T-cell Stemness 持续存活：靶向克隆性造血染色质调节因子促进CD8 T细胞之干细胞 Xingjian Qiu; Aaron Yang; Amanda C. Poholek Cancer Res (2025) 85 (2): 200–202. Review（综述） 4 Cancer-Related Cognitive Impairment and the Potential of Dietary Interventions for the Prevention and Mitigation of Neurodegeneration 癌症相关认知障碍与饮食干预用以预防和减轻神经元变性的潜力 Sylvia L. Crowder; Lisa M. Gudenkauf; Aasha I. Hoogland; Hyo S. Han; Brent J. Small; Tiffany L. Carson; Nathan H. Parker; Margaret Booth-Jones; Heather S.L. Jim Cancer Res (2025) 85 (2): 203–217. Resource Report（资源报告） 5 BEEx Is an Open-Source Tool That Evaluates Batch Effects in Medical Images to Enable Multicenter Studies BEEx是一个开源工具，用于评估医学图像中的批处理效应，以实现多中心研究 Yuxin Wu; Xiongjun Xu; Yuan Cheng; Xiuming Zhang; Fanxi Liu; Zhenhui Li; Lei Hu; Anant Madabhushi; Peng Gao; Zaiyi Liu; Cheng Lu Cancer Res (2025) 85 (2): 218–230. Cancer Biology（癌症生物学） 6 FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma FOXR2靶向LHX6+/DLX+神经谱系以驱动中枢神经系统神经母细胞瘤 Selin Jessa; Antonella De Cola; Bhavyaa Chandarana; Michael McNicholas; Steven Hébert; Adam Ptack; Damien Faury; Jessica W. Tsai; Andrey Korshunov; Timothy N. Phoenix; Benjamin Ellezam; David T.W. Jones; Michael D. Taylor; Pratiti Bandopadhayay; Manav Pathania; Nada Jabado; Claudia L. Kleinman Cancer Res (2025) 85 (2): 231–250. 7 KRAS Loss of Heterozygosity Promotes MAPK-Dependent Pancreatic Ductal Adenocarcinoma Initiation and Induces Therapeutic Sensitivity to MEK Inhibition KRAS杂合子缺失促进MAPK依赖性胰腺导管腺癌的发生，并诱导对MEK抑制的治疗敏感性 Sigrid K. Fey; Arafath K. Najumudeen; Dale M. Watt; Laura M. Millett; Catriona A. Ford; Kathryn Gilroy; Rosalin J. Simpson; Kathy McLay; Rosanna Upstill-Goddard; David Chang; William Clark; Colin Nixon; Joanna L. Birch; Simon T. Barry; Jennifer P. Morton; Andrew D. Campbell; Owen J. Sansom Cancer Res (2025) 85 (2): 251–262. 8 Ephrin A1 Stimulates CCL2 Secretion to Facilitate Premetastatic Niche Formation and Promote Gastric Cancer Liver Metastasis Ephrin A1刺激CCL2分泌促进转移前微环境形成并促进胃癌肝转移 Yun Cui; Yongxia Chang; Xixi Ma; Meng Sun; Yuliang Huang; Feng Yang; Shuang Li; Wei Zhuo; Wei Liu; Bo Yang; Aifu Lin; Guangshuo Ou; Yuehong Yang; Shanshan Xie; Tianhua Zhou Cancer Res (2025) 85 (2): 263–276. Cancer Immunology（癌症免疫学） 9 Spatial and Single-Cell Analyses Reveal Heterogeneity of DNAM-1 Receptor–Ligand Interactions That Instructs Intratumoral γδT-cell Activity 空间和单细胞分析揭示指示肿瘤内γδ t细胞活性的DNAM-1受体-配体相互作用的异质性 Xiaolin Wang; Hui Wang; Zhengjing Lu; Xiangjun Liu; Wenjia Chai; Wei Wang; Jun Feng; Shen Yang; Wei Yang; Haiyan Cheng; Chenghao Chen; Shihan Zhang; Nian Sun; Qiaoyin Liu; Qiliang Li; Wenqi Song; Fang Jin; Qi Zeng; Shengcai Wang; Yan Su; Huanmin Wang; Xin Ni; Jingang Gui Cancer Res (2025) 85 (2): 277–298. 10 ACE2 Enhances Sensitivity to PD-L1 Blockade by Inhibiting Macrophage-Induced Immunosuppression and Angiogenesis ACE2通过抑制巨噬细胞诱导的免疫抑制和血管生成增强对PD-L1阻断的敏感性 Peiyi Xie; Lei Guo; Qiang Yu; Yufei Zhao; Mincheng Yu; Hui Wang; Mengyuan Wu; Wenxin Xu; Min Xu; Xiao-Dong Zhu; Yongfeng Xu; Yong-Sheng Xiao; Cheng Huang; Jian Zhou; Jia Fan; Mien-Chie Hung; Huichuan Sun; Qing-Hai Ye; Bo Zhang; Hui Li Cancer Res (2025) 85 (2): 299–313. Cancer Metabolism and Molecular Mechanisms（癌症代谢与分子机制） 11 PHGDH Induction by MAPK Is Essential for Melanoma Formation and Creates an Actionable Metabolic Vulnerability MAPK诱导的PHGDH对黑色素瘤形成是必需的，并产生可操作的代谢脆弱性 Neel Jasani; Xiaonan Xu; Benjamin Posorske; Yumi Kim; Kaizhen Wang; Olga Vera; Kenneth Y. Tsai; Gina M. DeNicola; Florian A. Karreth Cancer Res (2025) 85 (2): 314–328. Therapeutic Development and Chemical Biology（治疗进展与生化学） 12 Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C–MHC I Complex Demonstrate the Antitumor Efficacy of Hapten-Based Strategies sotorasib修饰的KRAS G12C-MHC I复合物的靶向治疗和结构表征证明了基于半抗原方法的抗肿瘤疗效 Apurva Pandey; Peter J. Rohweder; Lieza M. Chan; Chayanid Ongpipattanakul; Dong hee Chung; Bryce Paolella; Fiona M. Quimby; Ngoc Nguyen; Kliment A. Verba; Michael J. Evans; Charles S. Craik Cancer Res (2025) 85 (2): 329–341. 13 An Autophagy-Targeting Chimera Induces Degradation of Androgen Receptor Mutants and AR-v7 in Castration-Resistant Prostate Cancer 在去势抵抗性前列腺癌中，靶向自噬的嵌合体诱导雄激素受体突变体和AR-v7的降解 Tae Hyun Bae; Ki Woon Sung; Tri M. Pham; Abdo J. Najy; Alaleh Zamiri; Hyejeong Jang; Su Ran Mun; Seongho Kim; Ha Kyoung Kwon; Yeon Sung Son; Dongping Shi; Steven Kregel; Elisabeth I. Heath; Michael L. Cher; Yong Tae Kwon; Hyeong-Reh Choi Kim Cancer Res (2025) 85 (2): 342–359. Translational Cancer Biology（癌症转化生物学） 14 The EP3–ZNF488 Axis Promotes Self-Renewal of Glioma Stem-Like Cells to Induce Resistance to Tumor Treating Fields EP3-ZNF488轴促进胶质瘤干样细胞的自我更新，诱导对肿瘤治疗领域的耐药性 Dongjiang Chen; Son B. Le; Harshit Manektalia; Tianyi Liu; Tarun E. Hutchinson; Adam O’Dell; Bodour Salhia; David D. Tran Cancer Res (2025) 85 (2): 360–377. Computational Cancer Biology and Technology（癌症生物学计算机与技术） 15 The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma 功能转录组学特征为多发性骨髓瘤的治疗方法提供信息 Praneeth Reddy Sudalagunta; Rafael R. Canevarolo; Mark B. Meads; Maria Silva; Xiaohong Zhao; Christopher L. Cubitt; Samer S. Sansil; Gabriel DeAvila; Raghunandan Reddy Alugubelli; Ryan T. Bishop; Alexandre Tungesvik; Qi Zhang; Oliver Hampton; Jamie K. Teer; Eric A. Welsh; Sean J. Yoder; Bijal D. Shah; Lori Hazlehurst; Robert A. Gatenby; Dane R. Van Domelen; Yi Chai; Feng Wang; Andrew DeCastro; Amanda M. Bloomer; Erin M. Siegel; Conor C. Lynch; Daniel M. Sullivan; Melissa Alsina; Taiga Nishihori; Jason Brayer; John L. Cleveland; William Dalton; Christopher J. Walker; Yosef Landesman; Rachid Baz; Ariosto S. Silva; Kenneth H. Shain Cancer Res (2025) 85 (2): 378–398. Correction（更正） 16 Correction: Mathematical Model-Driven Deep Learning Enables Personalized Adaptive Therapy 更正：数学模型驱动的深度学习实现了个性化自适应治疗 Kit Gallagher; Maximilian A.R. Strobl; Derek S. Park; Fabian C. Spoendlin; Robert A. Gatenby; Philip K. Maini; Alexander R.A. Anderson Cancer Res (2025) 85 (2): 399. Editor’s Note（编者按） 17 Editor’s Note: Mitochondrially Targeted p53 Has Tumor Suppressor Activities In vivo 编者按：线粒体靶向p53在体内具有肿瘤抑制活性 Flaminia Talos; Oleksi Petrenko; Patricio Mena; Ute M. Moll Cancer Res (2025) 85 (2): 400. Cancer Res[Jour] AND 85[volume] AND 3 [issue] 癌症研究 85卷 3期 https://aacrjournals.org/cancerres/issue/ In the Spotlight(焦点) 1 In Search of Representative Translational Cancer Model Systems 寻找具有代表性的转化癌症模型系统 Hannah E. Trembath; Philip M. Spanheimer Cancer Res (2025) 85 (3): 407–409 2 Adapt or Perish: Efficient Selenocysteine Insertion Is Critical for Metastasizing Cancer Cells 适应或危险：有效的硒代半胱氨酸插入对转移癌症细胞至关重要 Namgyu Lee; Dohoon Kim Cancer Res (2025) 85 (3): 410–412 Review(综述) 3 Fungal Influences on Cancer Initiation, Progression, and Response to Treatment 真菌对癌症发生、进展和治疗反应的影响 Hazrat Bilal; Muhammad Nadeen Khan; Sabir Khan; Muhammad Shafiq; Wenjie Fang; Yuebin Zeng; Yangzhong Guo; Xiaohui Li; Bing Zhao; Qiao-Li Lv; Bin Xu Cancer Res (2025) 85 (3): 413–423 Cancer Biology(癌症生物学) 4 Conditional Activation of c-MYC in Distinct Catecholaminergic Cells Drives Development of Neuroblastoma or Somatostatinoma 不同儿茶酚胺能细胞中c-MYC的条件激活驱动神经母细胞瘤或生长抑素瘤的发展 Tingting Wang; Lingling Liu; Jie Fang; Hongjian Jin; Sivaraman Natarajan; Heather Sheppard; Meifen Lu; Gregory Turner; Thomas Confer; Melissa Johnson; Jeffrey Steinberg; Larry Ha; Nour Yadak; Richa Jain; David J. Picketts; Xiaotu Ma; Andrew Murphy; Andrew M. Davidoff; Evan S. Glazer; John Easton; Xiang Chen; Ruoning Wang; Jun Yang Cancer Res (2025) 85 (3): 424–441 5 Mutant PP2A Induces IGFBP2 Secretion to Promote Development of High-Grade Uterine Cancer 突变体PP2A诱导IGFBP2分泌促进高级别子宫癌的发展 Terrance J. Haanen, III; Sophie Boock; Catherine G. Callahan; Irene Peris; Kaitlin P. Zawacki; Brynne Raines; Charles A. Nino; Brian Tran; Alexis Harold; Gabrielle Hodges Onishi; Matthew Hinderman; Amanda Dowdican; Wei Huang; Derek J. Taylor; Sarah E. Taylor; Mark W. Jackson; Analisa DiFeo; Caitlin M. O’Connor; Goutham Narla Cancer Res (2025) 85 (3): 442–461 Cancer Immunology(癌症免疫学) 6 Scavenger Receptor CD36 in Tumor-Associated Macrophages Promotes Cancer Progression by Dampening Type-I IFN Signaling 肿瘤相关巨噬细胞中的清除剂受体CD36通过抑制I型IFN信号传导促进癌症进展 Ziyan Xu; Alexandra Kuhlmann-Hogan; Shihao Xu; Hubert Tseng; Dan Chen; Shirong Tan; Ming Sun; Victoria Tripple; Marcus Bosenberg; Kathryn Miller-Jensen; Susan M. Kaech Cancer Res (2025) 85 (3): 462–476 7 Ferroptotic Neutrophils Induce Immunosuppression and Chemoresistance in Breast Cancer 嗜铁中性粒细胞诱导癌症的免疫抑制和化疗耐药性 Wenfeng Zeng; Ruihua Zhang; Penghan Huang; Minxia Chen; Houying Chen; Xin Zeng; Jiang Liu; Jiahui Zhang; Di Huang; Liyan Lao Cancer Res (2025) 85 (3): 477–496 8 The circRNA cEMSY Induces Immunogenic Cell Death and Boosts Immunotherapy Efficacy in Lung Adenocarcinoma circRNA-cEMSY诱导肺腺癌免疫原性细胞死亡并提高免疫治疗效果 Yijian Zhang; Xuming Song; Yipeng Feng; Yuxian Qian; Bing Chen; Te Zhang; Hui Wang; Yuzhong Chen; Xinnian Yu; Hanlin Ding; Rutao Li; Pengfei Ge; Lin Xu; Gaochao Dong; Feng Jiang Cancer Res (2025) 85 (3): 497–514 Cancer Metabolism and Molecular Mechanisms(癌症代谢和分子机制) 9 CSTF2 Supports Hypoxia Tolerance in Hepatocellular Carcinoma by Enabling m6A Modification Evasion of PGK1 to Enhance Glycolysis CSTF2通过使m6A修饰避开PGK1来增强糖酵解，从而支持肝细胞癌的缺氧耐受 Qiangnu Zhang; Yusen Zhang; Chuli Fu; Xiaoyan He; Zuotian Huang; Geyan Wu; Teng Wei; Wen Jin; Lesen Yan; Meilong Wu; Gongze Peng; LinLan Fan; Mingyue Li; Yuehua Guo; Jiangang Bi; Yu Bai; Stephanie Roessler; Guang-Rong Yan; Liping Liu Cancer Res (2025) 85 (3): 515–534 10 PRDM16 Induces Methylation of FLT3 to Promote FLT3-ITD Signaling and Leukemia Progression PRDM16诱导FLT3甲基化促进FLT3-ITD信号传导和白血病进展 Fengxian Zhai; Guozheng Pan; Lei Xue; Can Cheng; Jiabei Wang; Yao Liu; Lianxin Liu Cancer Res (2025) 85 (3): 535–550 Translational Cancer Biology(转化癌症生物学) 11 Kinome-Focused CRISPR-Cas9 Screens in African Ancestry Patient-Derived Breast Cancer Organoids Identify Essential Kinases and Synergy of EGFR and FGFR1 Inhibition 在非洲裔患者来源的乳腺癌类器官中进行以Kinome为中心的CRISPR-Cas9 筛选，鉴定出关键激酶以及 EGFR 和 FGFR1 抑制的协同作用 Florencia P. Madorsky Rowdo; Rachel Martini; Sarah E. Ackermann; Colin P. Tang; Marvel Tranquille; Adriana Irizarry; Ilkay Us; Omar Alawa; Jenna E. Moyer; Michael Sigouros; John Nguyen; Majd Al Assaad; Esther Cheng; Paula S. Ginter; Jyothi Manohar; Brian Stonaker; Richard Boateng; Joseph K. Oppong; Ernest K. Adjei; Baffour Awuah; Ishmael Kyei; Francis S. Aitpillah; Michael O. Adinku; Kwasi Ankomah; Ernest B. Osei-Bonsu; Kofi K. Gyan; Syed Hoda; Lisa Newman; Juan Miguel Mosquera; Andrea Sboner; Olivier Elemento; Lukas E. Dow; Melissa B. Davis; M. Laura Martin Cancer Res (2025) 85 (3): 551–566 12 Modeling Drug Responses and Evolutionary Dynamics Using Patient-Derived Xenografts Reveals Precision Medicine Strategies for Triple-Negative Breast Cancer 利用患者来源的异种移植物建立药物反应和进化动力学模型揭示了癌症三阴性乳腺癌的精确医学策略 Abigail Shea; Yaniv Eyal-Lubling; Daniel Guerrero-Romero; Raquel Manzano Garcia; Wendy Greenwood; Martin O’Reilly; Dimitra Georgopoulou; Maurizio Callari; Giulia Lerda; Sophia Wix; Agnese Giovannetti; Riccardo Masina; Elham Esmaeilishirazifard; Wei Cope; Alistair G. Martin; Ai Nagano; Lisa Young; Steven Kupczak; Yi Cheng; Helen Bardwell; Elena Provenzano; Justine Kane; Jonny Lay; Louise Grybowicz; Karen McAdam; Carlos Caldas; Jean Abraham; Oscar M. Rueda; Alejandra Bruna Cancer Res (2025) 85 (3): 567–584 13 Loss of CDKN2A Enhances the Efficacy of Immunotherapy in EGFR-Mutant Non–Small Cell Lung Cancer CDKN2A缺失增强EGFR突变型非小细胞肺癌免疫治疗效果 Simeng Wang; Jia-Cheng Lai; Yu Li; Chengfang Tang; Jiajia Lu; Min Han; Xianjiang Ye; Lina Jia; Wei Cui; Jingyu Yang; Chunfu Wu; Lihui Wang Cancer Res (2025) 85 (3): 585–601 Cancer Landscapes(癌症特征) 14 Multiomics Analysis Reveals Molecular Changes during Early Progression of Precancerous Lesions to Lung Adenocarcinoma in Never-Smokers 多组学分析揭示不吸烟者癌前病变向肺腺癌早期发展过程中的分子变化 Yun-Ching Chen; Chia-Lang Hsu; Hui-Min Wang; Shang-Gin Wu; Yih-Leong Chang; Jin-Shing Chen; Yu-Ching Wu; Yen-Ting Lin; Ching-Yao Yang; Mong-Wei Lin; Jang-Ming Lee; Shuenn-Wen Kuo; Ke-Cheng Chen; Hsao-Hsun Hsu; Pei-Ming Huang; Yen-Lin Huang; Chong-Jen Yu; Mehdi Pirooznia; Bevan E. Huang; Rob Yang; Jin-Yuan Shih; Pan-Chyr Yang Cancer Res (2025) 85 (3): 602–617 Computational Cancer Biology and Technology(计算癌症生物学与技术) 15 Fluorescence Lifetime Imaging Enables In Vivo Quantification of PD-L1 Expression and Intertumoral Heterogeneity 荧光寿命成像能够在体内定量PD-L1表达和肿瘤间异质性 Rahul Pal; Murali Krishnamoorthy; Aya Matsui; Homan Kang; Satoru Morita; Hajime Taniguchi; Tatsuya Kobayashi; Atsuyo Morita; Hak Soo Choi; Dan G. Duda; Anand T.N. Kumar Cancer Res (2025) 85 (3): 618–632 Cancer Res[Jour] AND 85[volume] AND 3_Supplement [issue] 癌症研究 85卷3期增刊 https://aacrjournals.org/cancerres/issue/85/3_Supplement Abstracts: AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; February 1-4, 2025; San Diego, CA 摘要：美国癌症研究协会之癌症研究特别会议：DNA甲基化、克隆造血与癌症；2025年2月1日至4日；加州，圣地亚哥  CLONAL HEMATOPOIESIS  克隆性造血 DNA METHYLATION IN A CHROMATIN CONTEXT  染色质背景下的DNA甲基化 INTERPRETING METHYLATION SIGNALS  解读甲基化信号 NEW CONCEPTS IN CANCER EPIGENETICS  癌症表观遗传学的新概念 NEW DNMTIS, COMBINATIONS, AND RESPONSES  新的DNMTIS、组合和反应 NORMAL AND ABNORMAL METHYLATION PATTERNS AND DETECTION  正常和异常甲基化模式和检测 ROLE OF DNA METHYLATION AND HYDROXYMETHYLATION IN IMMUNE CELL FUNCTION DNA甲基化和羟甲基化在免疫细胞功能中的作用 OTHER TOPICS 其他主题 Cancer Res[Jour] AND 85[volume] AND 4 [issue] 癌症研究 85卷4期 https://aacrjournals.org/cancerres/issue/ In the Spotlight(亮点) 1 Deterministic Role of FOXF2 in Organ-Specific Macrometastasis Transition FOXF2在器官特异性大转移的转化中的决定性作用 Igor L. Bado Cancer Res (2025) 85 (4): 639–641 2 MHC Hammer Decodes HLA Disruption in Tumors MHC Hammer解码HLA在肿瘤中的破坏 Timothy Sears; Hannah Carter Cancer Res (2025) 85 (4): 642–643 Cancer Biology(癌症生物学) 3 Breast Cancer Subtype–Specific Organotropism Is Dictated by FOXF2-Regulated Metastatic Dormancy and Recovery 乳腺癌亚型特异性器官亲和性由FOXF2调控的转移性休眠和恢复决定 Wen-Jing Jiang; Tian-Hao Zhou; Huan-Jing Huang; Lin-Sen Li; Hao Tan; Rui Zhang; Qing-Shan Wang; Yu-Mei Feng Cancer Res (2025) 85 (4): 644–659 4 HBV Remodels PP2A Complexes to Rewire Kinase Signaling in Hepatocellular Carcinoma HBV重组PP2A复合物以重新连接肝细胞癌中的激酶信号 Rigney E. Turnham; Adriana Pitea; Gwendolyn M. Jang; Zhong Xu; Huat Chye Lim; Alex L. Choi; John Von Dollen; Rebecca S. Levin; James T. Webber; Elizabeth McCarthy; Junjie Hu; Xiaolei Li; Li Che; Ananya Singh; Alex Yoon; Gary K.L. Chan; Robin K. Kelley; Danielle L. Swaney; Wei Zhang; Sourav Bandyopadhyay; Fabian J. Theis; Manon Eckhardt; Xin Chen; Kevan M. Shokat; Trey Ideker; Nevan J. Krogan; John D. Gordan Cancer Res (2025) 85 (4): 660–674 5 Chromatin Helicase CHD6 Establishes Proinflammatory Enhancers and Is a Synthetic Lethal Target in FH-Deficient Renal Cell Carcinoma 染色质解旋酶CHD6在FH-缺陷肾细胞癌中建立促炎增强因子并成为合成致死靶点 Juan Jin; Jun Luo; Xiaodong Jin; Kiat Shenq Lim; Yang He; Jiawei Ding; Yan Shen; Yuchen Hou; Hanqing Liu; Xiaoyu Zhu; Jing Zhao; Wenjie Zhou; Hai Huang; Yi Gao; Jun Xiao; Hongchao He; Qunyi Li; Lianxin Liu; Li Chen; Qiang He; Chuanjie Zhang Cancer Res (2025) 85 (4): 675–691 Cancer Immunology(癌症免疫学) 6 Adenosine Uptake through the Nucleoside Transporter ENT1 Suppresses Antitumor Immunity and T-cell Pyrimidine Synthesis 腺苷通过核苷转运蛋白ENT1摄取抑制抗肿瘤免疫和T细胞嘧啶合成 David Allard; Jeanne Cormery; Salma Bricha; Camille Fuselier; Farnoosh Abbas Aghababazadeh; Lucie Giraud; Emma Skora; Benjamin Haibe-Kains; John Stagg Cancer Res (2025) 85 (4): 692–703 7 Mapping of the T-cell Landscape of Biliary Tract Cancer Unravels Anatomic Subtype-Specific Heterogeneity 胆道癌的T细胞图谱揭示解剖亚型特异性异质性 Jianhua Nie; Shuyuan Zhang; Ying Guo; Caiqi Liu; Jiaqi Shi; Haotian Wu; Ruisi Na; Yingjian Liang; Shan Yu; Fei Quan; Kun Liu; Mingwei Li; Meng Zhou; Ying Zhao; Xuehan Li; Shengnan Luo; Qian Zhang; Guangyu Wang; Yanqiao Zhang; Yuanfei Yao; Yun Xiao; Sheng Tai; Tongsen Zheng Cancer Res (2025) 85 (4): 704–722 Cancer Metabolism and Molecular Mechanisms(癌症代谢和分子机制) 8 Energy Stress–Induced circEPB41(2) Promotes Lipogenesis in Hepatocellular Carcinoma 能量应激诱导的环EPB41(2)促进肝细胞癌的脂肪生成 Yang Yang; Jingjing Luo; Zhongyu Wang; Kaiyue Liu; Keyi Feng; Fang Wang; Yide Mei Cancer Res (2025) 85 (4): 723–738 9 PTBP1 Lactylation Promotes Glioma Stem Cell Maintenance through PFKFB4-Driven Glycolysis PTBP1乳糖化通过PFKFB4驱动的糖酵解促进胶质瘤干细胞的维持 Zijian Zhou; Xianyong Yin; Hao Sun; Jiaze Lu; Yuming Li; Yang Fan; Peiwen Lv; Min Han; Jing Wu; Shengjie Li; Zihao Liu; Hongbo Zhao; Haohan Sun; Hao Fan; Shan Wang; Tao Xin Cancer Res (2025) 85 (4): 739–757 Therapeutic Development and Chemical Biology(治疗进展与生物化学) 10 A Potent, Selective, Small-Molecule Inhibitor of DHX9 Abrogates Proliferation of Microsatellite Instable Cancers with Deficient Mismatch Repair 一种强效、选择性、小分子DHX9抑制剂可抑制错配修复缺陷的微卫星不稳定癌症的增殖 Jennifer Castro; Matthew H. Daniels; David Brennan; Brian Johnston; Deepali Gotur; Young-Tae Lee; Kevin E. Knockenhauer; Chuang Lu; Jie Wu; Sunaina Nayak; Cindy Collins; Rishabh Bansal; Shane M. Buker; April Case; Julie Liu; Shihua Yao; Brian A. Sparling; E. Allen Sickmier; Serena J. Silver; Stephen J. Blakemore; P. Ann Boriack-Sjodin; Kenneth W. Duncan; Scott Ribich; Robert A. Copeland Cancer Res (2025) 85 (4): 758–776 11 Imlunestrant Is an Oral, Brain-Penetrant Selective Estrogen Receptor Degrader with Potent Antitumor Activity in ESR1 Wild-Type and Mutant Breast Cancer Imlunestrant是一种口服的，脑渗透的选择性雌激素受体降解剂，对ESR1野生型和突变型乳腺癌具有有效的抗肿瘤活性 Shripad V. Bhagwat; Cecilia Mur; Matthew Vandekopple; Baohui Zhao; Weihua Shen; Carlos Marugán; Andrew Capen; Lisa Kindler; Jennifer R. Stephens; Lysiane Huber; Mark A. Castanares; David Garcia-Tapia; Jeff D. Cohen; Jolie Bastian; Brian Mattioni; Eunice Yuen; Thomas K. Baker; Vivian Rodriguez Cruz; Dongling Fei; Jason R. Manro; Nicholas Pulliam; Michele S. Dowless; Maria Jesus Ortiz Ruiz; Chunping Yu; Loredana Puca; Anke Klippel; Francesca Bacchion; Roohi Ismail-Khan; Vanessa Rodrik-Outmezguine; Sheng-Bin Peng; María Jose Lallena; Xueqian Gong; Alfonso de Dios Cancer Res (2025) 85 (4): 777–790 Translational Cancer Biology(癌症转化生物学) 12 Plasma Cell–Free DNA Chromatin Immunoprecipitation Profiling Depicts Phenotypic and Clinical Heterogeneity in Advanced Prostate Cancer 血浆游离 DNA 染色质免疫沉淀图谱描绘了晚期前列腺癌的表型和临床异质性 Joonatan Sipola; Aslı D. Munzur; Edmond M. Kwan; Clara C.Y. Seo; Benjamin J. Hauk; Karan Parekh; Yi Jou (Ruby) Liao; Cecily Q. Bernales; Gráinne Donnellan; Ingrid Bloise; Emily Fung; Sarah W.S. Ng; Gang Wang; Gillian Vandekerkhove; Matti Nykter; Matti Annala; Corinne Maurice-Dror; Kim N. Chi; Cameron Herberts; Alexander W. Wyatt; David Y. Takeda Cancer Res (2025) 85 (4): 791–807 13 Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma 靶向PREX2/RAC1/PI3Kβ信号轴赋予黑色素瘤临床相关治疗方法的敏感性 Catriona A. Ford; Dana Koludrovic; Patricia P. Centeno; Mona Foth; Elpida Tsonou; Nikola Vlahov; Nathalie Sphyris; Kathryn Gilroy; Courtney Bull; Colin Nixon; Bryan Serrels; Alison F. Munro; John C. Dawson; Neil O. Carragher; Valeria Pavet; David C. Hornigold; Philip D. Dunne; Julian Downward; Heidi C.E. Welch; Simon T. Barry; Owen J. Sansom; Andrew D. Campbell Cancer Res (2025) 85 (4): 808–824 Corrections(更正) 14 Correction: p38γ MAPK Is Essential for Aerobic Glycolysis and Pancreatic Tumorigenesis 更正：p38γ MAPK是有氧糖酵解和胰腺肿瘤发生至关重要 Fang Wang; Xiao-Mei Qi; Ryan Wertz; Matthew Mortensen; Catherine Hagen; John Evans; Yuri Sheinin; Michael James; Pengyuan Liu; Susan Tsai; James Thomas; Alexander Mackinnon; Michael Dwinell; Charles R. Myers; Ramon Bartrons Bach; Liwu Fu; Guan Chen Cancer Res (2025) 85 (4): 825 15 Correction: Long Noncoding RNA MIR17HG Promotes Colorectal Cancer Progression via miR-17-5p 更正：长非编码RNA MIR17HG通过miR-17-5p促进结直肠癌癌症进展 Jie Xu; Qingtao Meng; Xiaobo Li; Hongbao Yang; Jin Xu; Na Gao; Hao Sun; Shenshen Wu; Giuseppe Familiari; Michela Relucenti; Haitao Zhu; Jiong Wu; Rui Chen Cancer Res (2025) 85 (4): 826 Cancer Res[Jour] AND 85[volume] AND 5[issue] 癌症研究85卷 5期 https://aacrjournals.org/cancerres/issue/ In the Spotlight（焦点） 1 Unlocking the Role of Senescent Cell–Derived Extracellular Vesicles in Immune-Mediated Tumor Suppression 解锁衰老细胞来源的细胞外囊泡在免疫介导的肿瘤抑制中的作用 Sofia Almeida; Sonia A. Melo Cancer Res (2025) 85 (5): 833–835. 2 Switching Drivers: Epigenetic Rewiring to Genetic Progression in Glioma 驱动转换：胶质瘤中从表观遗传重塑到遗传进展 Kristen L. Drucker; Robert B. Jenkins; Daniel Schramek Cancer Res (2025) 85 (5): 836–837. Review（综述） 3 DOT1L Mediates Stem Cell Maintenance and Represents a Therapeutic Vulnerability in Cancer DOT1L介导干细胞的维持并成为癌症的治疗靶点 Hetakshi Kurani; Joyce M. Slingerland Cancer Res (2025) 85 (5): 838–847. Resource Report（资源报告） 4 spatialGE Is a User-Friendly Web Application That Facilitates Spatial Transcriptomics Data Analysis spatialGE：一个对用户友好的网络应用程序，以便于空间转录组数据分析 Oscar E. Ospina; Roberto Manjarres-Betancur; Guillermo Gonzalez-Calderon; Alex C. Soupir; Inna Smalley; Kenneth Y. Tsai; Joseph Markowitz; Mariam L. Khaled; Ethan Vallebuona; Anders E. Berglund; Steven A. Eschrich; Xiaoqing Yu; Brooke L. Fridley Cancer Res (2025) 85 (5): 848–858. Cancer Biology（癌症生物学） 5 Senescent Cell–Derived Extracellular Vesicles Inhibit Cancer Recurrence by Coordinating Immune Surveillance 衰老细胞来源的细胞外囊泡通过协调免疫监视抑制癌症复发 Tahereh Ziglari; Nicholas L. Calistri; Jennifer M. Finan; Daniel S. Derrick; Ernesto S. Nakayasu; Meagan C. Burnet; Jennifer E. Kyle; Matthew Hoare; Laura M. Heiser; Ferdinando Pucci Cancer Res (2025) 85 (5): 859–874. 6 Gain-of-Function Chromatin Remodeling Activity of Oncogenic FOXL2C134W Reprograms Glucocorticoid Receptor Occupancy to Drive Granulosa Cell Tumors 致癌性FOXL2C134W的获得性功能染色质重塑活性通过重新编码糖皮质激素受体占位来驱动颗粒细胞瘤 Thomas Welte; Veena K. Vuttaradhi; Eleonora Y. Khlebus; Allison Brodsky; Alejandra Flores Legarreta; Joseph Celestino; Reid T. Powell; Clifford C. Stephan; Nghi Nguyen; Jian Li; Shiro Takamatsu; Katherine Calzoncinth; Anil K. Sood; David M. Gershenson; P. Andrew Futreal; Barrett Lawson; R. Tyler Hillman Cancer Res (2025) 85 (5): 875–893. 7 Accumulation of CD38 in Hybrid Epithelial/Mesenchymal Cells Promotes Immune Remodeling and Metastasis in Breast Cancer 杂交上皮/间质细胞中CD38的累积可促进免疫重塑和乳腺癌转移 Tanvi H. Visal; Recep Bayraktar; Petra den Hollander; Michael A. Attathikhun; Tieling Zhou; Jing Wang; Li Shen; Corina-Elena Minciuna; Meng Chen; Elizve Barrientos-Toro; Harsh Batra; Maria Gabriela Raso; Fei Yang; Edwin R. Parra; Aysegul A. Sahin; George A. Calin; Sendurai A. Mani Cancer Res (2025) 85 (5): 894–911. Cancer Immunology（癌症免疫学） 8 SEMA3G–NRP1 Signaling Functions as an Immune Checkpoint That Enables Tumor Immune Evasion by Impairing T-cell Cytotoxicity SEMA3G-NRP1信号功能可作为免疫检测点，其通过损害T细胞毒性使肿瘤逃避免疫 Hao Chi; Shouyan Deng; Ke Xu; Yibo Zhang; Teng Song; Jianghong Yu; Yiting Wang; Jiayang Liu; Yuan Zhang; Jiawei Shi; Yungang Wang; Jie Xu Cancer Res (2025) 85 (5): 912–924. 9 Targeting Arachidonic Acid Metabolism Enhances Immunotherapy Efficacy in ARID1A-Deficient Colorectal Cancer 靶向花生四烯酸代谢可增强ARID1A缺陷型结直肠癌的免疫治疗效果 Luying Cui; Ruiqi Liu; Shuling Han; Chunhui Zhang; Bojun Wang; Yuli Ruan; Xuefan Yu; Yien Li; Yuanfei Yao; Xin Guan; Yuanyu Liao; Dan Su; Yue Ma; Shuijie Li; Chao Liu; Yanqiao Zhang Cancer Res (2025) 85 (5): 925–941. Cancer Metabolism and Molecular Mechanisms（癌症代谢与分子机制） 10 Selenoprotein O Promotes Melanoma Metastasis and Regulates Mitochondrial Complex II Activity 硒蛋白O促进黑色素瘤转移并调节线粒体复合体II活性 Luiza Martins Nascentes Melo; Marie Sabatier; Vijayashree Ramesh; Krystina J. Szylo; Cameron S. Fraser; Alex Pon; Evann C. Mitchell; Kelly A. Servage; Gabriele Allies; Isa V. Westedt; Feyza Cansiz; Jonathan Krystkiewicz; Andrea Kutritz; Dirk Schadendorf; Sean J. Morrison; Jessalyn M. Ubellacker; Anju Sreelatha; Alpaslan Tasdogan Cancer Res (2025) 85 (5): 942–955. Therapeutic Development and Chemical Biology（治疗学进展与生物化学） 11 A Pan-RAS Inhibitor with a Unique Mechanism of Action Blocks Tumor Growth and Induces Antitumor Immunity in Gastrointestinal Cancer 一种具有独特作用机制的泛RAS抑制剂可阻断胃肠癌症肿瘤生长并诱导抗肿瘤免疫 Jeremy B. Foote; Tyler E. Mattox; Adam B. Keeton; Xi Chen; Forrest T. Smith; Kristy Berry; Thomas W. Holmes; Junwei Wang; Chung-hui Huang; Antonio Ward; Amit K. Mitra; Veronica Ramirez-Alcantara; Cherlene Hardy; Karianne G. Fleten; Kjersti Flatmark; Karina J. Yoon; Sujith Sarvesh; Ganji P. Nagaraju; Dhana Sekhar Reddy Bandi; Yulia Y. Maxuitenko; Jacob Valiyaveettil; Julienne L. Carstens; Donald J. Buchsbaum; Jennifer Yang; Gang Zhou; Elmar Nurmemmedov; Ivan Babic; Vadim Gaponeko; Hazem Abdelkarim; Michael R. Boyd; Greg Gorman; Upender Manne; Sejong Bae; Bassel F. El-Rayes; Gary A. Piazza Cancer Res (2025) 85 (5): 956–972. 12 Antibody–Drug Conjugates Targeting the EGFR Ligand Epiregulin Elicit Robust Antitumor Activity in Colorectal Cancer 针对EGFR配体表皮调节素的抗体-药物偶联物在结直肠癌中显示出强大的抗肿瘤活性 Joan Jacob; Yasuaki Anami; Peyton C. High; Zhengdong Liang; Shraddha Subramanian; Sukhen C. Ghosh; Solmaz AghaAmiri; Cara Guernsey-Biddle; Ha Tran; Julie Rowe; Ali Azhdarinia; Kyoji Tsuchikama; Kendra S. Carmon Cancer Res (2025) 85 (5): 973–986. Computational Cancer Biology and Technology（计算癌症生物学与技术） 13 Spatiotemporal Profiling Defines Persistence and Resistance Dynamics during Targeted Treatment of Melanoma 时空特征分析定义了黑色素瘤靶向治疗期间持久性和耐药性动力学 Jill C. Rubinstein; Sergii Domanskyi; Todd B. Sheridan; Brian Sanderson; SungHee Park; Jessica Kaster; Haiyin Li; Olga Anczukow; Meenhard Herlyn; Jeffrey H. Chuang Cancer Res (2025) 85 (5): 987–1002. Editor’s Note（编者注） 14 Editor’s Note: PTEN Loss Contributes to Erlotinib Resistance in EGFR-Mutant Lung Cancer by Activation of Akt and EGFR 编辑注：PTEN缺失通过激活Akt和EGFR导致EGFR突变型肺癌对厄洛替尼耐药 Martin L. Sos; Mirjam Koker; Barbara A. Weir; Stefanie Heynck; Rosalia Rabinovsky; Thomas Zander; Jens M. Seeger; Jonathan Weiss; Florian Fischer; Peter Frommolt; Kathrin Michel; Martin Peifer; Craig Mermel; Luc Girard; Michael Peyton; Adi F. Gazdar; John D. Minna; Levi A. Garraway; Hamid Kashkar; William Pao; Matthew Meyerson; Roman K. Thomas Cancer Res (2025) 85 (5): 1003. Cancer Res[Jour] AND 85[volume] AND 5_Supplement[issue] 癌症研究85卷 5期增刊 https://aacrjournals.org/cancerres/issue/85/5_Supplement Abstracts: AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; March 11-13, 2025; Boston, MA 摘要：《癌症研究》之美国癌症研究协会特别会议：癌症中的功能与基因组学精准医学：不同视角，共同目标；2025年3月11-13日；波士顿，马萨诸塞州 CHALLENGES IN TISSUE ACQUISITION AND HANDLING FOR PRECISION MEDICINE 精准医学中组织获取与处理的挑战 CHALLENGES OF INTRA-TUMOR AND INTRA-PATIENT HETEROGENEITY FOR PRECISION MEDICINE 精准医学中肿瘤内和患者内异质性的挑战 CLINICAL TRIAL DESIGN FOR OPTIMAL IMPLEMENTATION OF PRECISION MEDICINE 为实现精准医学最优化的临床试验设计 FUNCTIONAL AND GENOMIC PRECISION MEDICINE IN BLOOD CANCERS 血液科恶性肿瘤中的功能与基因组学精准医学 FUNCTIONAL AND GENOMIC PRECISION MEDICINE IN SOLID TUMORS 实体瘤中的功能与基因组学精准医学 IMMUNOTHERAPY-PREDICTIVE BIOMARKERS 免疫治疗预测生物标志物 KEYNOTE LECTURE 主题演讲 MACHINE LEARNING TO INTEGRATE MULTIPLE DATA LAYERS 整合多层数据的机器学习 NEW OMICS FOR PRECISION MEDICINE 精准医学的新组学 REGULATORY AND NON-REGULATORY CHALLENGES TO THE WIDE ADOPTION OF PRECISION DIAGNOSTICS 精准诊断广泛采用中的监管与非监管挑战 VERTEBRATE MODELS FOR MODELING DISEASE AND GUIDING THERAPY 用于疾病建模和指导治疗的脊椎动物模型 OTHER TOPICS 其他主题 Cancer Res[Jour] AND 85[volume] AND 6[issue] 癌症研究 85卷 6期 https://aacrjournals.org/cancerres/issue/ In the Spotlight（焦点） 1 CAR-T Entering a New “Phase”: Improving CAR-T Function by Harnessing Phase Separation CAR-T 进入新“阶段”：利用相分离改善 CAR-T 功能 Xiaolei Su Cancer Res (2025) 85 (6): 1011–1012. 2 Breaking the Rhythm: Harnessing the Menstrual Cycle for Better Chemotherapy 打破节奏：利用月经周期提高化疗效果 Pranay Dey; Cathrin Brisken Cancer Res (2025) 85 (6): 1013–1014. Resource Report（资源报告） 3 Comparative Single-Cell Transcriptomics of Human Neuroblastoma and Preclinical Models Reveals Conservation of an Adrenergic Cell State 人类神经母细胞瘤与临床前模型的单细胞转录组学比较揭示了肾上腺素能细胞状态的保守性 Bethel Tesfai Embaie; Hirak Sarkar; Adele M. Alchahin; Jörg Otte; Thale Kristin Olsen; Conny Tümmler; Polina Kameneva; Artem V. Artemov; Natalia Akkuratova; Igor Adameyko; Jan-Bernd Stukenborg; Malin Wickström; Per Kogner; John Inge Johnsen; Shenglin Mei; Peter V. Kharchenko; Ninib Baryawno Cancer Res (2025) 85 (6): 1015–1034. Cancer Biology（癌症生物学） 4 CLK1 Activates YAP to Promote Intrahepatic Cholangiocarcinogenesis CLK1激活YAP促进肝内胆管癌发生 Shuai Xue; Xiangzheng Chen; Guoteng Qiu; Haotian Liao; Zeyuan Qiang; Zheng Zhang; Xuping Feng; Lin Xu; Rui Xie; Hongyu Zhou; Jiwei Huang; Yong Zeng; Haichuan Wang Cancer Res (2025) 85 (6): 1035–1048. 5 MICAL2 Promotes Pancreatic Cancer Growth and Metastasis MICAL2促进胰腺癌的生长和转移 Bharti Garg; Sohini Khan; Asimina S. Courelli; Ponmathi Panneerpandian; Deepa Sheik Pran Babu; Evangeline S. Mose; Kevin Christian Montecillo Gulay; Shweta Sharma; Divya Sood; Alexander T. Wenzel; Alexei Martsinkovskiy; Nirakar Rajbhandari; Jay Patel; Dawn Jaquish; Edgar Esparza; Katelin Jaque; Neetu Aggarwal; Guillem Lambies; Anthony D’Ippolito; Kathryn Austgen; Brian Johnston; David A. Orlando; Gun Ho Jang; Steven Gallinger; Elliot Goodfellow; Pnina Brodt; Cosimo Commisso; Pablo Tamayo; Jill P. Mesirov; Hervé Tiriac; Andrew M. Lowy Cancer Res (2025) 85 (6): 1049–1063. 6 Hypoxia-Induced Senescent Fibroblasts Secrete IGF1 to Promote Cancer Stemness in Esophageal Squamous Cell Carcinoma 缺氧诱导的衰老成纤维细胞分泌IGF1促进食管鳞状细胞癌的癌干性 Zhengjie Ou; Liang Zhu; Xinjie Chen; Tianyuan Liu; Guoyu Cheng; Rucheng Liu; Shaosen Zhang; Wen Tan; Dongxin Lin; Chen Wu Cancer Res (2025) 85 (6): 1064–1081. Cancer Immunology（癌症免疫学） 7 Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy 髓系细胞诱导B细胞和CD4+T滤泡辅助细胞浸润和激活，使脑转移瘤对联合免疫治疗敏感 Toshifumi Ninomiya; Naoya Kemmotsu; Fumiaki Mukohara; Masaki Magari; Ai Miyamoto; Youki Ueda; Takamasa Ishino; Joji Nagasaki; Tomohiro Fujiwara; Hidetaka Yamamoto; Hidetoshi Hayashi; Kota Tachibana; Joji Ishida; Yoshihiro Otani; Shota Tanaka; Shinichi Toyooka; Isamu Okamoto; Yosuke Togashi Cancer Res (2025) 85 (6): 1082–1096. Cancer Metabolism and Molecular Mechanisms（癌症代谢与分子机制） 8 SNHG17 Reprograms Energy Metabolism of Breast Cancer by Activating Mitochondrial DNA Transcription SNHG17通过激活线粒体DNA转录重塑乳腺癌的能量代谢 Lin Gao; Jingyi Huang; Jinquan Xia; Pan Zhao; Shaowei Dong; Wei Jiang; Qianqian Zhou; Zhenglei Xu; Hui Luo; Wenbin Zhou; Jichao Sun; Guangsuo Wang; Qingshan Geng; Jigang Wang; Chang Zou Cancer Res (2025) 85 (6): 1097–1112. 9 MTHFD2 Enhances cMYC O-GlcNAcylation to Promote Sunitinib Resistance in Renal Cell Carcinoma MTHFD2增强cMYC的O-GlcNAcylation，促进肾细胞癌对舒尼替尼的耐药 Jinwen Liu; Gaowei Huang; Hao Lin; Rui Yang; Wenhao Zhan; Cheng Luo; Yukun Wu; Lingwu Chen; Xiaopeng Mao; Junxing Chen; Bin Huang Cancer Res (2025) 85 (6): 1113–1129. Translational Cancer Biology（癌症转化生物学） 10 Immune Checkpoint Blockade Delays Cancer Development and Extends Survival in DNA Polymerase Mutator Syndromes 免疫检查点阻断可延缓DNA聚合酶突变综合征中的癌症进展并延长生存期 Akshada Sawant; Fuqian Shi; Eduardo Cararo Lopes; Zhixian Hu; Somer Abdelfattah; Jennele Baul; Jesse R. Powers; Christian S. Hinrichs; Joshua D. Rabinowitz; Chang S. Chan; Edmund C. Lattime; Shridar Ganesan; Eileen P. White Cancer Res (2025) 85 (6): 1130–1144. 11 Oxidative Phosphorylation Is a Metabolic Vulnerability of Endocrine Therapy–Tolerant Persister Cells in ER+ Breast Cancer 氧化磷酸化是ER+乳腺癌中内分泌治疗耐受持久细胞的代谢弱点 Steven Tau; Mary D. Chamberlin; Huijuan Yang; Jonathan D. Marotti; Patricia C. Muskus; Alyssa M. Roberts; Melissa M. Carmichael; Lauren Cressey; Christo Philip C. Dragnev; Eugene Demidenko; Riley A. Hampsch; Shannon M. Soucy; Fred W. Kolling; Kimberley S. Samkoe; James V. Alvarez; Arminja N. Kettenbach; Todd W. Miller Cancer Res (2025) 85 (6): 1145–1161. 12 Evolutionary Pressures Shape Undifferentiated Pleomorphic Sarcoma Development and Radiotherapy Response 进化压力塑造未分化多形性肉瘤的进展和放疗反应 Erik S. Blomain; Shaghayegh Soudi; Ziwei Wang; Anish Somani; Ajay Subramanian; Serey C.L. Nouth; Eniola Oladipo; Christin New; Deborah E. Kenney; Neda Nemat-Gorgani; Thomas Kindler; Raffi S. Avedian; Robert J. Steffner; David G. Mohler; Susan M. Hiniker; Alexander L. Chin; Anusha Kalbasi; Michael S. Binkley; Marius Fried; Matthias M. Gaida; Matt van de Rijn; Everett J. Moding Cancer Res (2025) 85 (6): 1162–1174. Retraction（撤回） 13 Retraction: Cell-Permeable NM23 Blocks the Maintenance and Progression of Established Pulmonary Metastasis 撤回：细胞通透型NM23可阻断已形成的肺转移持续和进展 Junghee Lim; Giyong Jang; Seeun Kang; Guewha Lee; Do Thi Thuy Nga; Do Thi Lan Phuong; Hyuncheol Kim; Wael El-Rifai; H. Earl Ruley; Daewoong Jo Cancer Res (2025) 85 (6): 1175. Cancer Res[Jour] AND 85[volume] AND 7[issue] 癌症研究85卷 7期 https://aacrjournals.org/cancerres/issue/ Priority Report(特邀报道) 1 ZNFX1 Functions as a Master Regulator of Epigenetically Induced Pathogen Mimicry and Inflammasome Signaling in Cancer 在癌症中作为表观遗传诱导的病原体模拟和炎症小体信号传导的主要调节因子的ZNFX1功能 Lora Stojanovic; Rachel Abbotts; Kaushelendra Tripathi; Collin M. Coon; Saranya Rajendran; Elnaz Abbasi Farid; Galen Hostetter; Joseph W. Guarnieri; Douglas C. Wallace; Sheng Liu; Jun Wan; Gennaro Calendo; Rebecca Marker; Zahra Gohari; Mohammed M.A. Inayatullah; Vijay K. Tiwari; Tanjina Kader; Sandro Santagata; Ronny Drapkin; Stefan Kommoss; Jacobus Pfisterer; Gottfried E. Konecny; Ryan Coopergard; Jean-Pierre J. Issa; Boris J.N. Winterhoff; Michael J. Topper; George E. Sandusky; Kathy D. Miller; Stephen B. Baylin; Kenneth P. Nephew; Feyruz V. Rassool Cancer Res (2025) 85 (7): 1183–1198 Cancer Biology(癌症生物学) 2 ST6GAL1-Mediated Sialylation of PECAM-1 Promotes a Transcellular Diapedesis–Like Process That Directs Lung Tropism of Metastatic Breast Cancer ST6GAL1 介导的 PECAM-1 唾液酰化促进了一种跨细胞渗出样过程，引导转移性乳腺癌的肺趋向性 Shih-Yin Chen; Pei-Lin He; Li-Yu Lu; Meng-Chieh Lin; Shih-Hsuan Chan; Jia-Shiuan Tsai; Wen-Ting Luo; Lu-Hai Wang; Hua-Jung Li Cancer Res (2025) 85 (7): 1199–1218 Cancer Immunology(癌症免疫学) 3 Comparison of Lean, Obese, and Weight-Loss Models Reveals TREM2 Deficiency Attenuates Breast Cancer Growth Uniquely in Lean Mice and Alters Clonal T-cell Populations 消瘦、肥胖和减肥模型的比较显示TREM2缺乏在消瘦小鼠中可特异性削弱乳腺癌生长并改变克隆T细胞群 Elysa W. Pierro; Matthew A. Cottam; Hanbing An; Brian D. Lehmann; Jennifer A. Pietenpol; Kathryn E. Wellen; Liza Makowski; Jeffrey C. Rathmell; Barbara Fingleton; Alyssa H. Hasty Cancer Res (2025) 85 (7): 1219–1235 4 Targeting ARPC1B Overcomes Immune Checkpoint Inhibitor Resistance in Glioblastoma by Reversing Protumorigenic Macrophage Polarization 靶向ARPC1B通过逆转促肿瘤型巨噬细胞极化克服胶质母细胞瘤对免疫检查点抑制剂的耐药性 Tianqi Liu; Tao Sun; Xin Chen; Jianqi Wu; Xiaoqian Sun; Xing Liu; Haixu Yan; Qiang Fu; Zirong Fan; Xiangyu Wang; Peng Cheng; Wen Cheng; Anhua Wu Cancer Res (2025) 85 (7): 1236–1252 Cancer Metabolism and Molecular Mechanisms(癌症代谢与分子机制) 5 Mutant KRAS and CK2 Cooperatively Stimulate SLC16A3 Activity to Drive Intrahepatic Cholangiocarcinoma Progression KRAS和CK2突变协同刺激SLC16A3活性以驱动肝内胆管癌进展 Ran Chen; Cuihong Ma; Haoran Qian; Xinyu Xie; Yuxue Zhang; Dayun Lu; Shunjie Hu; Mao Zhang; Fen Liu; Yunhao Zou; Qiang Gao; Hu Zhou; Hailong Liu; Moubin Lin; Gaoxiang Ge; Daming Gao Cancer Res (2025) 85 (7): 1253–1269 6 Targeting TUT1 Depletes Tri-snRNP Pools to Suppress Splicing and Inhibit Pancreatic Cancer Cell Survival 靶向TUT1使Tri-snRNP池耗尽抑制剪接同时抑制胰腺癌细胞存活 Ziwei Guo; Junran Huang; Zhi J. Lu; Yongsheng Shi; Charles J. David; Mo Chen Cancer Res (2025) 85 (7): 1270–1286 Therapeutic Development and Chemical Biology(治疗学进展与生物化学) 7 STING Agonist VB-85247 Induces Durable Antitumor Immune Responses by Intravesical Administration in a Non–Muscle-Invasive Bladder Cancer STING激动剂VB-85247通过膀胱内给药诱导非肌层侵袭性膀胱癌患者持久性抗肿瘤免疫反应 Miglena G. Prabagar; Michael McQueney; Venu Bommireddy; Rachael Siegel; Gary L. Schieven; Ku Lu; Ruziboy Husanov; Reema Deepak; David Diller; Chia-Yu Huang; Eli Mordechai; Rukiye-Nazan Eraslan Cancer Res (2025) 85 (7): 1287–1296 Translational Cancer Biology(癌症转化生物学) 8 Profiling the Activity of the Potent and Highly Selective CDK2 Inhibitor BLU-222 Reveals Determinants of Response in CCNE1-Aberrant Ovarian and Endometrial Tumors 强效高选择性CDK2抑制剂BLU-222的活性分析揭示了CCNE1异常卵巢和子宫内膜肿瘤反应的决定因素 Nealia C. House; Victoria E. Brown; Maxine Chen; Liang Yuan; Sydney L. Moore; Jian Guo; Yoon Jong Choi; Lakshmi Muthuswamy; Scott Ribich; Philip Ramsden; Kerrie L. Faia Cancer Res (2025) 85 (7): 1297–1309 9 Tumor Suppressors Condition Differential Responses to the Selective CDK2 Inhibitor BLU-222 肿瘤抑制因子状态对选择性CDK2抑制剂BLU-222的不同反应 Adam P. Dommer; Vishnu Kumarasamy; Jianxin Wang; Thomas N. O’Connor; Michelle Roti; Sidney Mahan; Karen McLean; Erik S. Knudsen; Agnieszka K. Witkiewicz Cancer Res (2025) 85 (7): 1310–1326 Convergence Science(融合医学) 10 Genomic Analysis Reveals Racial and Age-Related Differences in the Somatic Landscape of Breast Cancer and the Association with Socioeconomic Factors 基因组分析揭示了与种族和年龄相关的乳腺癌体细胞特征差异及其与社会经济因素的关联 Sarah C. Van Alsten; Michael I. Love; Benjamin C. Calhoun; Eboneé N. Butler; Charles M. Perou; Katherine A. Hoadley; Melissa A. Troester Cancer Res (2025) 85 (7): 1327–1340 Correction(更正) 11 Correction: Comprehensive DNA Methylation Analysis Indicates That Pancreatic Intraepithelial Neoplasia Lesions Are Acinar-Derived and Epigenetically Primed for Carcinogenesis 更正：综合DNA甲基化分析表明胰腺上皮内瘤变病变是腺泡衍生的，并在表观遗传上为癌变做好了准备 Emily K.W. Lo; Brian M. Mears; H. Carlo Maurer; Adrian Idrizi; Kasper D. Hansen; Elizabeth D. Thompson; Laura D. Wood; Ralph H. Hruban; Kenneth P. Olive; Andrew P. Feinberg Cancer Res (2025) 85 (7): 1341 Editor's Note(编者注) 12 Editor’s Note: TRIM59 Promotes Gliomagenesis by Inhibiting TC45 Dephosphorylation of STAT3 编者注：TRIM59通过抑制STAT3的TC45去磷酸化促进胶质瘤形成 Youzhou Sang; Yanxin Li; Lina Song; Angel A. Alvarez; Weiwei Zhang; Deguan Lv; Jianming Tang; Feng Liu; Zhijie Chang; Shigetsugu Hatakeyama; Bo Hu; Shi-Yuan Cheng; Haizhong Feng Cancer Res (2025) 85 (7): 1342 Cancer Res[Jour] AND 85[volume] AND 8[issue] 癌症研究 85卷8期 https://aacrjournals.org/cancerres/issue/ In the Spotlight（焦点） 1 Condensates as a Culprit in RAS Activation and Inhibitor Resistance 冷凝物是RAS激活与抑制剂耐药的“罪魁祸首” Hannah C. Bergo; Logan B. Leak; Trever G. Bivona Cancer Res (2025) 85 (8): 1349–1351. 2 Distinct States of Nuclear Speckles Emerge as New Predictors of Cancer Prognosis 核斑点出现的不同状态成为癌症预后的新型预测因子 Lisa Martina; Michał Małszycki; Tuğçe Aktaş Cancer Res (2025) 85 (8): 1352–1353. Review（综述） 3 Circulating Tumor Microenvironment in Metastasis 转移中的循环肿瘤微环境 Rui Tang; Shujuan Luo; Hui Liu; Yan Sun; Manran Liu; Lu Li; Haoyu Ren; Martin K. Angele; Nikolaus Börner; Keda Yu; Zufeng Guo; Guobing Yin; Haojun Luo Cancer Res (2025) 85 (8): 1354–1367. Cancer Biology（癌症生物学） 4 SMAD4 and KRAS Status Shapes Cancer Cell–Stromal Cross-Talk and Therapeutic Response in Pancreatic Cancer SMAD4和KRAS状态决定胰腺癌中癌细胞-间质相互作用及治疗反应 Eloise G. Lloyd; Muntadher Jihad; Judhell S. Manansala; Wenlong Li; Priscilla S.W. Cheng; Gianluca Mucciolo; Marta Zaccaria; Sara Pinto Teles; Joaquín Araos Henríquez; Sneha Harish; Rebecca Brais; Sally Ashworth; Weike Luo; Paul M. Johnson; Lisa Veghini; Mireia Vallespinos; Vincenzo Corbo; Giulia Biffi Cancer Res (2025) 85 (8): 1368–1389. 5 Lineage Tracing and Single-Cell RNA Sequencing Reveal a Common Transcriptional State in Breast Cancer Tumor–Initiating Cells Characterized by IFN/STAT1 Activity 谱系追踪和单细胞RNA测序揭示乳腺癌肿瘤一种由IFN/STAT1活性表征的起始细胞中的共同转录状态 Eric P. Souto; Ping Gong; John D. Landua; Ramakrishnan Rajaram Srinivasan; Abhinaya Ganesan; Lacey E. Dobrolecki; Stephen C. Purdy; Xingxin Pan; Michael Zeosky; Anna Chung; S. Stephen Yi; Heide L. Ford; Michael T. Lewis Cancer Res (2025) 85 (8): 1390–1409. 6 Replication-Poison Treatment in BRCA1-Deficient Breast Cancer Causes MRE11 Over-Resection That Induces Single-Stranded DNA Accumulation and Mitotic Catastrophe BRCA1缺陷型乳腺癌中的复制毒素治疗导致MRE11过度切除，进而诱发单链DNA积累和有丝分裂灾难 Imene Tabet; Esin Orhan; Ermes Candiello; Lise Fenou; Carolina Velázquez; Beatrice Orsetti; Geneviève Rodier; William Jacot; Cyril Ribeyre; Claude Sardet; Charles Theillet Cancer Res (2025) 85 (8): 1410–1423. Cancer Immunology（癌症免疫学） 7 Single-Cell Analyses Reveal a Functionally Heterogeneous Exhausted CD8+ T-cell Subpopulation That Is Correlated with Response to Checkpoint Therapy in Melanoma 单细胞分析揭示了功能异质性的耗竭型CD8+ T细胞亚群，该亚群与黑色素瘤对检查点疗法的反应相关 Kelly M. Mahuron; Osmaan Shahid; Prachi Sao; Clinton Wu; Alexandra M. Haugh; Laura A. Huppert; Lauren S. Levine; Margaret M. Lowe; Michael Alvarado; Markee Micu; Katy K. Tsai; Melissa Chow; Meromit Singer; Jason M. Schenkel; Arlene H. Sharpe; Michael D. Rosenblum; Kristen E. Pauken; Adil I. Daud Cancer Res (2025) 85 (8): 1424–1440. 8 An Immune Subtype Classification System Enables the Development of Strategies to Predict and Enhance Immunotherapy Responses in Colorectal Cancer 免疫亚型分类系统助力制定策略，以预测并增强结直肠癌对免疫疗法的反应 Dingchang Li; Xianqiang Liu; Wenxing Gao; Wen Zhao; Shuaifei Ji; Sizhe Wang; Jinran Yang; Dingling Li; Zhengyao Chang; Yi Chen; Xu Sun; Jingcheng Zhou; Yanan Jiao; Xiaohui Du; Guanglong Dong Cancer Res (2025) 85 (8): 1441–1458. 9 Ribosomal RNA Biosynthesis Functionally Programs Tumor-Associated Macrophages to Support Breast Cancer Progression 核糖体RNA生物合成在功能上调控肿瘤相关巨噬细胞以支持乳腺癌进展 Brandon J. Metge; Li’an Williams; Courtney A. Swain; Dominique C. Hinshaw; Amr R. Elhamamsy; Dongquan Chen; Rajeev S. Samant; Lalita A. Shevde Cancer Res (2025) 85 (8): 1459–1478. Cancer Metabolism and Molecular Mechanisms（癌症代谢与分子机制） 10 Concurrent Inhibition of the RAS-MAPK Pathway and PIKfyve Is a Therapeutic Strategy for Pancreatic Cancer 同时抑制RAS-MAPK通路和PIKfyve是胰腺癌的一种治疗策略 Jonathan M. DeLiberty; Mallory K. Roach; Clint A. Stalnecker; Ryan Robb; Elyse G. Schechter; Noah L. Pieper; Khalilah E. Taylor; Lily M. Pita; Runying Yang; Scott Bang; Kristina Drizyte-Miller; Sarah E. Ackermann; Sheila R. Nicewarner Peña; Elisa Baldelli; Sophia M. Min; David H. Drewry; Emanuel F. Petricoin, III; John P. Morris, IV; Channing J. Der; Adrienne D. Cox; Kirsten L. Bryant Cancer Res (2025) 85 (8): 1479–1495. 11 JMJD6 Rewires ATF4-Dependent Glutathione Metabolism to Confer Ferroptosis Resistance in SPOP-Mutated Prostate Cancer JMJD6重编码ATF4依赖性谷胱甘肽代谢，赋予SPOP突变型前列腺癌铁死亡抗性 Chuanjie Zhang; Jiawei Ding; Kiat Shenq Lim; Wenjie Zhou; Wenyu Miao; Siqi Wu; Hanqing Liu; Da Huang; Chufeng Chen; Hongchao He; Jun Xiao; Dan-feng Xu; Yan Shen; Hai Huang; Yi Gao Cancer Res (2025) 85 (8): 1496–1513. Translational Cancer Biology（癌症转化生物学） 12 The Brain-Penetrant Pan-ErbB Inhibitor Poziotinib Effectively Targets HER2+ Breast Cancer Brain Metastases 脑穿透性泛ErbB抑制剂波齐替尼可有效靶向HER2+乳腺癌脑转移 Danyyl Ippolitov; Yi-Han Lin; Jeremy Spence; Aleksandra Glogowska; Thatchawan Thanasupawat; Jason Beiko; Marc R. Del Bigio; Xin Xu; Amy Q. Wang; Darian Williams; Raul Calvo; Abhijeet Kapoor; Juan J. Marugan; Mark J. Henderson; Thomas Klonisch; Sabine Hombach-Klonisch Cancer Res (2025) 85 (8): 1514–1529. Computational Cancer Biology and Technology（癌症计算生物学与技术） 13 Characterization of an Enhancer RNA Signature Reveals Treatment Strategies for Improving Immunotherapy Efficacy in Cancer 增强子RNA特征分析揭示癌症免疫疗法增效治疗策略 Chenyang Zhang; Yan-Yan Chen; Shuyu Chen; Yunzhe Wang; Yifan Yuan; Xiwen Yang; Wei Hu; Bo Chen; Zengxin Qi; Jason T. Huse; Yun Liu; Bo Wen; Xiuping Liu; Leng Han; Yuxiang Wang; Zhao Zhang Cancer Res (2025) 85 (8): 1530–1543. Convergence Science（融合医学） 14 Interactions between Ploidy and Resource Availability Shape Clonal Evolution in Glioblastoma 倍性与资源可用性之间的相互作用塑造了胶质母细胞瘤中的克隆进化 Zuzanna Nowicka; Frederika Rentzeperis; Vural Tagal; Jamie K. Teer; Didem Ilter; Richard J. Beck; Jackson P. Cole; Ana Forero Pinto; Joanne D. Tejero; Elisa Scanu; Thomas Veith; William Dominguez-Viqueira; Konstantin Maksin; Francisco Carrillo-Perez; Olivier Gevaert; Xiaonan Xu; Florian A. Karreth; Mahmoud A. Abdalah; Giada Fiandaca; Stefano Pasetto; Sandhya Prabhakaran; Andrew Schultz; Awino Maureiq E. Ojwang’; Jill S. Barnholtz-Sloan; Joaquim M. Farinhas; Ana P. Gomes; Parag Katira; Noemi Andor Cancer Res (2025) 85 (8): 1544–1559. Cancer Res[Jour] AND 85[volume] AND 8_Supplement_1[issue] 癌症研究 85卷 8期增刊1期 https://aacrjournals.org/cancerres/issue/85/8_Supplement_1 Proceedings: AACR Annual Meeting 2025; April 25-30, 2025; Chicago, Illinois; Part 1 (Regular Abstracts) 会议录：美国癌症研究协会（AACR）2025年年会；2025年4月25日至30日；伊利诺伊州芝加哥市；第一部分（常规摘要） AACR PROJECT GENIE 美国癌症研究协会（AACR）基因组项目 BIOINFORMATICS, COMPUTATIONAL BIOLOGY, SYSTEMS BIOLOGY, AND CONVERGENT SCIENCE 生物信息学、计算生物学、系统生物学及融合医学 CHEMISTRY 化学 CLINICAL RESEARCH 临床研究 ENDOCRINOLOGY 内分泌学 EXPERIMENTAL AND MOLECULAR THERAPEUTICS 实验与分子治疗学 IMMUNOLOGY 免疫学 MOLECULAR / CELLULAR BIOLOGY AND GENETICS 分子/细胞生物学与遗传学 MULTIDISCIPLINARY 多学科 POPULATION SCIENCES 公共医学 PREVENTION, EARLY DETECTION, AND INTERCEPTION 预防、早期检测与干预 REGULATORY SCIENCE AND POLICY 监管医学与政策 SCIENCE AND HEALTH POLICY 科学与健康政策 TUMOR BIOLOGY 肿瘤生物学 Cancer Res[Jour] AND 85[volume] AND 8_Supplement_2[issue] 癌症研究 85卷8期增刊2期 https://aacrjournals.org/cancerres/issue/85/8_Supplement_2 Proceedings: AACR Annual Meeting 2025; April 25-30, 2025; Chicago, Illinois; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) 会议录：美国癌症研究协会（AACR）2025年年会；2025年4月25日 - 30日；美国伊利诺伊州芝加哥；第二部分（最新突破、临床试验及特邀摘要专场） BIOINFORMATICS / COMPUTATIONAL BIOLOGY / SYSTEMS BIOLOGY / CONVERGENT SCIENCE 生物信息学/计算生物学/系统生物学/融合科学 CHEMISTRY, DRUG DEVELOPMENT 化学、药物研发 CLINICAL RESEARCH 临床研究 CLINICAL TRIALS 临床试验 DRUG DEVELOPMENT 药物研发 EXPERIMENTAL AND MOLECULAR THERAPEUTICS 实验与分子治疗学 EXPERIMENTAL AND MOLECULAR THERAPEUTICS, CHEMISTRY 实验与分子治疗学、化学 IMMUNOLOGY 免疫学 MOLECULAR/CELLULAR BIOLOGY AND GENETICS 分子/细胞生物学与遗传学 MULTIDISCIPLINARY 多学科交叉 POPULATION SCIENCES 公共医学 PREVENTION / EARLY DETECTION / INTERCEPTION 预防/早期检测/干预 SCIENCE AND HEALTH POLICY 科学与健康政策 SURVIVORSHIP 肿瘤生存者关怀 TUMOR BIOLOGY 肿瘤生物学 Cancer Res[Jour] AND 85[volume] AND 9[issue] 癌症研究 85卷 9期 https://aacrjournals.org/cancerres/issue/ Obituary（讣告） 1 Nathan Berger, MD: In Memoriam (1941–2024) 内森·伯格医学博士：悼念（1941–2024） Kathryn H. Schmitz; Linda Nebeling Cancer Res (2025) 85 (9): 1567. In the Spotlight（焦点） 2 Launching SMART 3D Cancer Models 推出SMART 3D癌症模型 Sam Ernst; Olivier De Wever Cancer Res (2025) 85 (9): 1568–1570. 3 The Biology in the Pattern: Metastatic Organotropism and Clinical Outcome Depend on DNA Damage Response and Immune Interactions in Pancreatic Cancer 模式中的生物学：胰腺癌的转移性器官趋向性和临床预后取决于DNA损伤反应和免疫相互作用 Aristeidis Papargyriou; Maximilian Reichert Cancer Res (2025) 85 (9): 1571–1573. 4 In the Right Place and the Right State: Spatial Cross-Talk and Immune State Dictate Leukemia Response to Immunotherapy 位置与状态并重：空间串扰和免疫状态决定白血病对免疫治疗的反应 Giorgio Orofino; Cristina Toffalori; Luca Vago Cancer Res (2025) 85 (9): 1574–1576. Resource Report（资源报告） 5 A 3D Self-Assembly Platform Integrating Decellularized Matrix Recapitulates In Vivo Tumor Phenotypes and Heterogeneity 整合脱细胞基质的3D自组装平台可重现体内肿瘤表型和异质性 Michael J. Buckenmeyer; Elizabeth A. Brooks; Madison S. Taylor; Ireolu K. Orenuga; Liping Yang; Ronald J. Holewinski; Thomas J. Meyer; Melissa Galloux; Marcial Garmendia-Cedillos; Thomas J. Pohida; Thorkell Andresson; Brad St. Croix; Matthew T. Wolf Cancer Res (2025) 85 (9): 1577–1595. Cancer Biology（癌症生物学） 6 CXCL10 Secreted by Pericytes Mediates TNFα-Induced Vascular Leakage in Tumors and Enhances Extravasation of Nanoparticle-Based Chemotherapeutics 周细胞分泌的CXCL10介导肿瘤坏死因子α（TNFα）诱导的肿瘤血管渗漏并增强基于纳米颗粒的化疗药物的渗出 Ann L.B. Seynhaeve; Hui Liu; Marjolein I. Priester; Mike Valentijn; Conny van Holten-Neelen; Rutger W.W. Brouwer; Mandy van Brakel; Willem A. Dik; Wilfred F.J. van IJcken; Reno Debets; Andrew P. Stubbs; Timo L.M. ten Hagen Cancer Res (2025) 85 (9): 1596–1610. 7 Tumorigenesis Driven by BRAFV600E Requires Secondary Mutations That Overcome Its Feedback Inhibition of RAC1 and Migration 由BRAFV600E驱动的肿瘤发生需要二次突变来克服其对RAC1的反馈抑制和迁移 Sunyana Gadal; Jacob A. Boyer; Simon F. Roy; Noah A. Outmezguine; Malvika Sharma; Hongyan Li; Ning Fan; Eric Chan; Yevgeniy Romin; Afsar Barlas; Qing Chang; Priya Pancholi; Neilawattie Merna Timaul; Michael Overholtzer; Rona Yaeger; Katia Manova-Todorova; Elisa de Stanchina; Marcus W. Bosenberg; Neal Rosen Cancer Res (2025) 85 (9): 1611–1627. 8 The Glycosyltransferase XYLT1 Activates NF-κB Signaling to Promote Metastasis of Early-Stage Lung Adenocarcinoma 糖基转移酶XYLT1激活NF-κB信号通路以促进早期肺腺癌的转移 Jian Han; Jianan Du; Xiangmeng Li; Qingbo Zhou; Jiayu Zeng; Jun-Tao Lin; Wenle Zhou; Jiayi Cai; Yaokai Ye; Bosui Yang; Junsheng Wang; Xiang Zhou; Rong Lian; Yi Yang; Xun Zhu; Hongyu Guan; Liping Liu; Junchao Cai; Jueheng Wu; Yun Li; Mengfeng Li; Han Tian Cancer Res (2025) 85 (9): 1628–1643. Cancer Immunology（癌症免疫学） 9 GLI2 Facilitates Tumor Immune Evasion and Immunotherapeutic Resistance by Coordinating WNT and Prostaglandin Signaling GLI2通过协调WNT和前列腺素信号传导促进肿瘤免疫逃逸和免疫治疗耐药性 Nicholas C. DeVito; Y-Van Nguyen; Michael Sturdivant; Michael P. Plebanek; Kaylee A. Villarreal; Nagendra Yarla; Vaibhav Jain; Michael Aksu; Georgia M. Beasley; Balamayooran Theivanthiran; Brent A. Hanks Cancer Res (2025) 85 (9): 1644–1662. Cancer Metabolism and Molecular Mechanisms（癌症代谢与分子机制） 10 Arginine Deprivation Induces Quiescence and Confers Vulnerability to Ferroptosis in Colorectal Cancer 精氨酸剥夺诱导结直肠癌细胞进入静止期并使其对铁死亡敏感 Yanyun Lin; Yanhong Zhang; Tianze Huang; Junguo Chen; Guanman Li; Bin Zhang; Liang Xu; Kai Wang; Hui He; Hao Chen; Danling Liu; Shuang Guo; Xiaosheng He; Ping Lan Cancer Res (2025) 85 (9): 1663–1679. Translational Cancer Biology（癌症转化生物学） 11 Longitudinal Profiling of Circulating Tumor DNA Reveals the Evolutionary Dynamics of Metastatic Prostate Cancer during Serial Therapy 循环肿瘤DNA纵向分析揭示了转移性前列腺癌在连续治疗过程中的进化动态 Yuehui Zhao; Naveen Ramesh; Ping Xu; Emi Sei; Min Hu; Shanshan Bai; Patricia Troncoso; Ana M. Aparicio; Christopher J. Logothetis; Paul G. Corn; Nicholas E. Navin; Amado J. Zurita Cancer Res (2025) 85 (9): 1680–1695. 12 Integrating Plasma Cell-Free DNA Fragment End Motif and Size with Genomic Features Enables Lung Cancer Detection 将血浆游离DNA片段末端基序和基因组特征相应尺寸相结合可实现肺癌检测 Tae-Rim Lee; Jin Mo Ahn; Junnam Lee; Dasom Kim; Juntae Park; Byeong-Ho Jeong; Dongryul Oh; Sang Man Kim; Gyou-Chul Jung; Beom Hee Choi; Min-Jung Kwon; Mengchi Wang; Michael Salmans; Andrew Carson; Bryan Leatham; Kristin Fathe; Byung In Lee; Byoungsok Jung; Chang-Seok Ki; Young Sik Park; Eun-Hae Cho Cancer Res (2025) 85 (9): 1696–1707. 13 Stabilization of RUNX1 Induced by O-GlcNAcylation Promotes PDGF-BB–Mediated Resistance to CDK4/6 Inhibitors in Breast Cancer O-GlcNAc糖基化诱导的RUNX1稳定性促进乳腺癌中血小板衍生生长因子BB（PDGF-BB）介导的对细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂的耐药性 Shuyan Zhou; Yi Zhang; Julie Belmar; Chunyan Hou; Yaqin Zhang; Changmin Peng; Yunxiao Meng; Zhuqing Li; Muhammad Jameel Mughal; Yanjun Gao; Edward Seto; Min Shen; Matthew D. Hall; Junfeng Ma; Cynthia X. Ma; Shunqiang Li; Wenge Zhu Cancer Res (2025) 85 (9): 1708–1724. Cancer Landscapes（癌症特征） 14 Genomic Characterization of High-Grade Serous Ovarian Carcinoma Reveals Distinct Somatic Features in Black Individuals 高级别浆液性卵巢癌的基因组特征揭示了黑人个体中独特的体细胞特征 Katherine A. Lawson-Michod; Jeffrey R. Marks; Lindsay J. Collin; David A. Nix; Natalie R. Davidson; Chad D. Huff; Yao Yu; Aaron Atkinson; Courtney E. Johnson; Lucas A. Salas; Lauren C. Peres; Casey S. Greene; Joellen M. Schildkraut; Jennifer A. Doherty Cancer Res (2025) 85 (9): 1725–1737. Corrections（更正） 15 Correction: Alternative Lengthening of Telomeres in Cancer Confers a Vulnerability to Reactivation of p53 Function 更正：癌症中的端粒替代性延长赋予p53功能重新激活的弱点 Shawn J. Macha; Balakrishna Koneru; Trevor A. Burrow; Charles Zhu; Dzmitry Savitski; Rakshandra L. Rahman; Catherine A. Ronaghan; Jonas Nance; Kristyn McCoy; Cody Eslinger; C. Patrick Reynolds Cancer Res (2025) 85 (9): 1738. 16 Correction: SCFFBXW7/GSK3β-Mediated GFI1 Degradation Suppresses Proliferation of Gastric Cancer Cells 更正：SCFFBXW7/GSK3β介导的GFI1降解抑制胃癌细胞的增殖 Xiaoling Kuai; Long Li; Ran Chen; Kangjunjie Wang; Min Chen; Binghau Cui; Yuxue Zhang; Junqiang Li; Hongwen Zhu; Hu Zhou; Jianfei Huang; Jun Qin; Zhiwei Wang; Wenyi Wei; Daming Gao Cancer Res (2025) 85 (9): 1739. Cancer Res[Jour] AND 85[volume] AND 10[issue] 癌症研究 85卷 10期 https://aacrjournals.org/cancerres/issue/ In the Spotlight（焦点） 1 Combining STING Agonists with PARP Inhibitors Mounts an NK-Dependent Defense against Therapy-Resistant Breast Cancer STING激动剂与PARP抑制剂联合使用可启动自然杀伤（NK）细胞依赖性防御机制对抗耐药性乳腺癌 Zahra Gohari; Lora Stojanovic; Feyruz V. Rassool Cancer Res (2025) 85 (10): 1747–1749. 2 From Fat Providers to Cancer Therapy: Adipocytes as Unexpected Allies 从脂肪“供应者”到癌症治疗：脂肪细胞成为意想不到的“盟友” Camille Attané; Catherine Muller Cancer Res (2025) 85 (10): 1750–1752. 3 “Dr. Jekyll and Mr. Hyde”: AT2 Cells in Lung Regeneration and Tumor Development “杰基尔博士与海德先生”：肺再生与肿瘤进展中的AT2细胞 Xinyuan Tong; Gen Lin; Hongbin Ji Cancer Res (2025) 85 (10): 1753–1754. Review（综述） 4 A Critical Appraisal of the Utility of Targeting Therapy-Induced Senescence for Cancer Treatment 靶向治疗诱导的细胞衰老在癌症治疗中的效用评估 Tareq Saleh; Edward F. Greenberg; Anthony C. Faber; Hisashi Harada; David A. Gewirtz Cancer Res (2025) 85 (10): 1755–1768. Resource Report（资源报告） 5 The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons of the Transcriptomic Landscapes Across Mouse Models 肺癌原位模型基因表达数据库支持跨小鼠模型转录组图谱的跨研究比较 Ling Cai; Fangjiang Wu; Qinbo Zhou; Ying Gao; Bo Yao; Ralph J. DeBerardinis; George K. Acquaah-Mensah; Vassilis Aidinis; Jennifer E. Beane; Shyam Biswal; Ting Chen; Carla P. Concepcion-Crisol; Barbara M. Grüner; Deshui Jia; Robert A. Jones; Jonathan M. Kurie; Min Gyu Lee; Per Lindahl; Yonathan Lissanu; Corina Lorz; David MacPherson; Rosanna Martinelli; Pawel K. Mazur; Sarah A. Mazzilli; Shinji Mii; Herwig P. Moll; Roger A. Moorehead; Edward E. Morrisey; Sheng Rong Ng; Matthew G. Oser; Arun R. Pandiri; Charles A. Powell; Giorgio Ramadori; Mirentxu Santos; Eric L. Snyder; Rocio Sotillo; Kang-Yi Su; Tetsuro Taki; Kekoa Taparra; Phuoc T. Tran; Yifeng Xia; J. Edward van Veen; Monte M. Winslow; Guanghua Xiao; Charles M. Rudin; Trudy G. Oliver; Yang Xie; John D. Minna Cancer Res (2025) 85 (10): 1769–1783. Cancer Biology（癌症生物学） 6 Palmitic Acid Accumulation Activates Fibroblasts and Promotes Matrix Stiffness in Colorectal Cancer 棕榈酸积累激活成纤维细胞并促进结直肠癌中的基质硬度 Shenghe Deng; Jun Wang; Falong Zou; Denglong Cheng; Mian Chen; Junnan Gu; Jianguo Shi; Jia Yang; Yifan Xue; Zhenxin Jiang; Le Qin; Fuwei Mao; Xiaona Chang; Xiu Nie; Li Liu; Yinghao Cao; Kailin Cai Cancer Res (2025) 85 (10): 1784–1802. 7 SMARCA4 Inhibits Breast Cancer Progression and Metastasis through RHOA Suppression SMARCA4通过抑制RHOA来抑制乳腺癌的进展和转移 Zheng Sun; Zhuo Li; Yong Wei; Lillian Xu; Xiang Hang; Yibin Kang Cancer Res (2025) 85 (10): 1803–1818. 8 Intratumoral Fusobacterium nucleatum Recruits Tumor-Associated Neutrophils to Promote Gastric Cancer Progression and Immune Evasion 瘤内核梭杆菌募集肿瘤相关中性粒细胞以促进胃癌进展和免疫逃逸 Tianhao Zhang; Ying Li; Ertao Zhai; Risheng Zhao; Yan Qian; Zhixin Huang; Yinan Liu; Zeyu Zhao; Xiang Xu; Jianqiu Liu; Zikang Li; Zhi Liang; Ran Wei; Linying Ye; Jinping Ma; Qingping Wu; Jianhui Chen; Shirong Cai Cancer Res (2025) 85 (10): 1819–1841. Cancer Immunology（癌症免疫学） 9 Macrophage-Derived Itaconate Suppresses Dendritic Cell Function to Promote Acquired Resistance to Anti–PD-1 Immunotherapy 巨噬细胞来源的衣康酸抑制树突状细胞功能，促进抗程序性死亡受体1（PD-1）免疫治疗的获得性耐药 Xiao Yang; Yue Deng; Ying Ye; Jingshu Meng; Mengyao Su; Wenwen Wei; You Qin; Haibo Zhang; Yu Tian; Suke Deng; Zhiyun Liao; Zhiyuan Zhou; Jie Li; Yan Hu; Bin Zhang; Yajie Sun; Lu Wen; Zhanjie Zhang; Fang Huang; Chao Wan; Kunyu Yang Cancer Res (2025) 85 (10): 1842–1856. Cancer Metabolism and Molecular Mechanisms（癌症代谢与分子机制） 10 De Novo Serine Synthesis Is a Metabolic Vulnerability That Can Be Exploited to Overcome Sunitinib Resistance in Advanced Renal Cell Carcinoma 从头合成丝氨酸是一种代谢弱点，可被利用来克服晚期肾细胞癌中的舒尼替尼耐药性 Manon Teisseire; Umakant Sahu; Julien Parola; Meng-Chen Tsai; Valérie Vial; Jérôme Durivault; Renaud Grépin; Yann Cormerais; Clément Molina; Arthur Gouraud; Gilles Pagès; Issam Ben-Sahra; Sandy Giuliano Cancer Res (2025) 85 (10): 1857–1873. Therapeutic Development and Chemical Biology（治疗进展与生物化学） 11 Engineered SH3-Derived Sherpabodies Function as a Modular Platform for Targeted T-cell Immunotherapy 人工改造的基于SH3结构域的Sherpabody可作为靶向T细胞免疫治疗的模块化平台 Rogelio A. Hernández-López; Tapio Kesti; Anna R. Mäkelä; Zhe Zhao; Wei Yu; Yurie Tonai; Hector J. Monzo; Kerttu Kalander; Sirpa Leppä; Päivi M. Ojala; Wendell A. Lim; Kalle Saksela Cancer Res (2025) 85 (10): 1874–1887. Translational Cancer Biology（癌症转化生物学） 12 Harnessing STING Signaling and Natural Killer Cells Overcomes PARP Inhibitor Resistance in Homologous Recombination–Deficient Breast Cancer 利用干扰素基因刺激因子（STING）信号传导和自然杀伤（NK）细胞克服同源重组缺陷型乳腺癌中的聚腺苷二磷酸核糖聚合酶（PARP）抑制剂耐药性 Flaminia Pedretti; Mohmed Abdalfttah; Benedetta Pellegrino; Francesca Mateo; Paula Martínez-Sanz; Andrea Herencia-Ropero; Andreu Òdena; Pau Clavell-Revelles; Giorgia Casali; Heura Domènech; Laia Monserrat; Dražen Papić; Alba Mas Malavila; Anna Pascual-Reguant; Herena Eixarch; Marta Guzmán; Olga Rodríguez; Judit Grueso; Sara Simonetti; Roberta Fasani; Paolo Nuciforo; Carmen Espejo; Stefan Florian; Miguel Ángel Pujana; Lara Nonell; Joan Seoane; Viia Valge-Archer; Mark J. O’Connor; Juan C. Nieto; Holger Heyn; Judith Balmaña; Alba Llop-Guevara; Violeta Serra Cancer Res (2025) 85 (10): 1888–1908. 13 FADD Functions as an Oncogene in Chr11q13.3-Amplified Head and Neck Squamous Cell Carcinoma FADD在Chr11q13.3扩增的头颈部鳞状细胞癌中发挥癌基因作用 Yang Zheng; Yinan Chen; Xiaoyan Meng; Li Zhang; Yanni Ma; Rong Zhou; Shuiting Fu; Heng Chen; Xinyang Xuanyuan; Ruixin Jiang; Pengcong Hou; Xiaomeng Song; Yanqiu Wang; Jingjing Sun; Wuchang Zhang; Jiang Li; Zhonglong Liu; Zhiyuan Zhang; Hanlin Zeng; Yue He Cancer Res (2025) 85 (10): 1909–1927. Cancer Landscapes（癌症特征） 14 Colorectal Tumors in Diverse Patient Populations Feature a Spectrum of Somatic Mutational Profiles 不同患者群体中的结直肠肿瘤具有不同的体细胞突变谱特征 Marco Matejcic; Jamie K. Teer; Hannah J. Hoehn; Diana B. Diaz; Kritika Shankar; Jun Gong; Nathalie T. Nguyen; Nicole C. Loroña; Domenico Coppola; Clifton G. Fulmer; Ozlen Saglam; Kun Jiang; W. Douglas Cress; Teresita Muñoz-Antonia; Idhaliz Flores; Edna R. Gordián; José A. Oliveras Torres; Seth I. Felder; Julian Sanchez; Jason B. Fleming; Erin M. Siegel; Jennifer A. Freedman; Julie Dutil; Mariana C. Stern; Brooke L. Fridley; Jane C. Figueiredo; Stephanie L. Schmit Cancer Res (2025) 85 (10): 1928–1944. Editor’s Note（编者注） 15 Editor’s Note: A Novel Role for Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6 as a Determinant of Gemcitabine Chemoresistance in Pancreatic Adenocarcinoma Cells Free 编者注：癌胚抗原相关细胞黏附分子6在胰腺腺癌细胞吉西他滨化疗耐药性中的新作用 Mark S. Duxbury; Hiromichi Ito; Eric Benoit; Talat Waseem; Stanley W. Ashley; Edward E. Whang Cancer Res (2025) 85 (10): 1945. Retractions（撤稿声明） 16 Retraction: HMGA1 Is a Determinant of Cellular Invasiveness and In vivo Metastatic Potential in Pancreatic Adenocarcinoma Free 撤稿声明：高迁移率族蛋白A1（HMGA1）是胰腺腺癌细胞侵袭性和体内转移潜能的决定因素 Siong-Seng Liau; Amarsanaa Jazag; Edward E. Whang Cancer Res (2025) 85 (10): 1946. 17 Retraction: Prostaglandin E2 Enhances Pancreatic Cancer Invasiveness through an Ets-1-Dependent Induction of Matrix Metalloproteinase-2 Free 撤稿声明：前列腺素E2通过Ets-1依赖性诱导基质金属蛋白酶-2来增强胰腺癌的侵袭性 Hiromichi Ito; Mark Duxbury; Eric Benoit; Thomas E. Clancy; Michael J. Zinner; Stanley W. Ashley; Edward E. Whang Cancer Res (2025) 85 (10): 1947. Cancer Res[Jour] AND 85[volume] AND 11[issue] 癌症研究85卷 11期 https://aacrjournals.org/cancerres/issue/ In the Spotlight（焦点） 1 Targeted Degradation of Mutant p53 Reverses the Pro-oncogenic Dominant-Negative Effect 靶向降解突变型p53可逆转其促癌的显性负效应 Jovanka Gencel-Augusto; Guillermina Lozano Cancer Res (2025) 85 (11): 1955–1956 2 PROX1: A Key Regulator of Hepatocyte Identity and Tumorigenesis PROX1：肝细胞特性及肿瘤发生的关键调控因子 Terence Kin Wah Lee; Stephanie Ma Cancer Res (2025) 85 (11): 1957–1959 Cancer Biology(癌症生物学) 3 FGFR2 Abrogation Intercepts Pancreatic Ductal Adenocarcinoma Development FGFR2缺失可阻断胰腺导管腺癌的进展 Claudia Tonelli; Astrid Deschênes; Victoria A. Gaeth; Amanda Jensen; Nandan Vithlani; Melissa A. Yao; Zhen Zhao; Youngkyu Park; David A. Tuveson Cancer Res (2025) 85 (11): 1960–1977 4 The Prolonged Half-Life of the p53 Missense Variant R248Q Promotes Accumulation and Heterotetramer Formation with Wild-Type p53 to Exert the Dominant-Negative Effect p53错义变异体R248Q的半衰期延长促进其与野生型p53的累积及异源四聚体形成，从而发挥显性负效应 Nancy Klemm; Roman R. Schimmer; Nils K. Konrad; Flavian Thelen; Jonas Fullin; Ebru Topçu; Christian Koch; Milena Treacy; Matthew Joseph Leventhal; Marco M. Bühler; Veronika Lysenko; Alexandre P.A. Theocharides; Kari J. Kurppa; Stefan Balabanov; Tuncay Baubec; Andrei V. Krivtsov; Peter G. Miller; Scott A. Armstrong; Benjamin L. Ebert; Markus G. Manz; Cesar Nombela-Arrieta; Steffen Boettcher Cancer Res (2025) 85 (11): 1978–1996 Cancer Immunology(癌症免疫学) 5 Mutation of SMARCA4 Induces Cancer Cell–Intrinsic Defects in the Enhancer Landscape and Resistance to Immunotherapy SMARCA4突变诱导癌细胞增强子特征内在缺陷及对免疫治疗的抵抗 Yawen Wang; Ismail M. Meraz; Md Qudratullah; Sasikumar Kotagiri; Yanyan Han; Yuanxin Xi; Jing Wang; Kadir C. Akdemir; Jack A. Roth; Yonathan Lissanu Cancer Res (2025) 85 (11): 1997–2013 6 Blocking the TCA Cycle in Cancer Cells Potentiates CD36+ T-cell–Mediated Antitumor Immunity by Suppressing ER Stress–Associated THBS2 Signaling 阻断癌细胞中的三羧酸循环通过抑制内质网应激相关的THBS2信号传导，增强CD36+ T细胞介导的抗肿瘤免疫 Jianqiang Yang; Fanghui Chen; Zhenzhen Fu; Fan Yang; Nabil F. Saba; Yong Teng Cancer Res (2025) 85 (11): 2014–2026 Cancer Metabolism and Molecular Mechanisms(癌症代谢和分子机制) 7 SMYD3 Activates Fatty Acid β-Oxidation to Promote Self-Renewal of Leukemia Stem Cells SMYD3激活脂肪酸β-氧化以促进白血病干细胞自我更新 Min Zhou; Zihao Wu; Fen Wei; Chen Duan; Xiaoying Lin; Waiyi Zou; Chang Liu; Jingxuan Pan; Yanli Jin Cancer Res (2025) 85 (11): 2027–2045 8 CRTC2 Forms Co-Condensates with YTHDF2 That Enhance Translational Efficiency of m6A-Modified mRNAs to Drive Hepatocarcinogenesis and Lenvatinib Resistance CRTC2与YTHDF2形成共凝集物，增强m6A修饰mRNA的转化效率，驱动肝细胞癌发生及乐伐替尼耐药 Meixi Wang; Fangdi Zou; Shengxin Wang; Yichen Yang; Cong Xia; Lu Chen; Ben Liu; Lian Li; Mulin Jun Li; Haixin Li; Weijie Song; Ruifang Niu; Zhiyong Yuan; Jie Yang; Xiangchun Li; Kexin Chen; Zhiqiang Wu; Zeyun Mi Cancer Res (2025) 85 (11): 2046–2066 Therapeutic Development and Chemical Biology(治疗进展与化学生物学) 9 An Anti-EGFR Antibody–Drug Radioconjugate Labeled with Actinium-225 Elicits Durable Antitumor Responses in KRAS- and BRAF-Mutant Colorectal Cancer 用锕-225标记的抗EGFR抗体-药物放射性偶联物在KRAS和BRAF突变型结直肠癌中诱导持久的抗肿瘤反应 Anjong Florence Tikum; Nikita W. Henning; Jessica Pougoue Ketchemen; Alireza Doroudi; Hanan Babeker; Fabrice Ngoh Njotu; Emmanuel Nwangele; Alissar Monzer; Bridget Gray; Emina Torlakovic; Maruti Uppalapati; Humphrey Fonge Cancer Res (2025) 85 (11): 2067–2080 Translational Cancer Biology(转化癌症生物学) 10 Perivascular Niche–Resident Alveolar Macrophages Promote Interstitial Pneumonitis Related to Trastuzumab Deruxtecan Treatment 血管周围间隙中的驻留肺泡巨噬细胞促进与德曲妥珠单抗治疗相关的间质性肺炎 Qing Wei; Teng Yang; Ziwen Zhang; Fei Wang; Yuxuan Yang; Jiayu Zhu; Xiu Zhu; Yuanzheng Li; Yun Xing; Ye Lu; Xuefei Tian; Mengyang Fan; Yuchao Zhang; Xiru Xue; Meng Li; Chuanfei Yu; Lan Wang; Takaya Shimura; Jianmin Fang; Zhiwei Cao; Jieer Ying; Peng Guo; Xiangdong Cheng Cancer Res (2025) 85 (11): 2081–2099 11 Targeting the SP/KLF Transcriptional Regulatory Network Synergizes with HDAC Inhibition to Impede Progression of H3K27M Diffuse Intrinsic Pontine Glioma 靶向SP/KLF转录调控网络与HDAC抑制协同作用，阻碍H3K27M弥漫性内生型桥脑胶质瘤的进展 Yu Kong; Fan Wang; Renwei Jing; Qian Zhao; Xuejiao Lv; Yingying Zhao; Ye Yuan; Xianyou Xia; Yu Sun; Yujie Tong; Han Yan; Qian Li; Ting Li; Lei Cao; Deng Liu; Dawei Huo; Shao-Kai Sun; Francisco Morís; Yujie Tang; Xudong Wu Cancer Res (2025) 85 (11): 2100–2116 12 Combining Apatinib and Oxaliplatin Remodels the Immunosuppressive Tumor Microenvironment and Sensitizes Desert-Type Gastric Cancer to Immunotherapy 阿帕替尼联合奥沙利铂重塑免疫抑制性肿瘤微环境，增强沙漠型胃癌对免疫治疗的敏感性 Guang-Tan Lin; Cheng Yan; Lu-Jie Li; Xiao-Wen Qiu; Yu-Xuan Zhao; Ju-Li Lin; Yu-Jing Chen; Chuan Feng; Shao-Qiong Chen; Jian-Wei Xie; Chao-Hui Zheng; Sachiyo Nomura; Chang-Ming Huang; Ping Li; Long-Long Cao Cancer Res (2025) 85 (11): 2117–2133 Editor’s Notes(编者按) 13 Editor’s Note: Normoxic Stabilization of Hypoxia-Inducible Factor-1α by Modulation of the Labile Iron Pool in Differentiating U937 Macrophages: Effect of Natural Resistance-Associated Macrophage Protein 1 编者按：通过调节分化中的U937巨噬细胞内不稳定铁池来稳定常氧条件下的缺氧诱导因子-1α：天然抗性相关巨噬细胞蛋白1的作用 Helen J. Knowles; David R. Mole; Peter J. Ratcliffe; Adrian L. Harris Cancer Res (2025) 85 (11): 2134 14 Editor’s Note: Effects of Transferrin Receptor Blockade on Cancer Cell Proliferation and Hypoxia-Inducible Factor Function and Their Differential Regulation by Ascorbate 编者按：转铁蛋白受体阻断对癌细胞增殖及缺氧诱导因子功能的影响及其受抗坏血酸的不同调控 Dylan T. Jones; Ian S. Trowbridge; Adrian L. Harris Cancer Res (2025) 85 (11): 2135 Cancer Res[Jour] AND 85[volume] AND 12[issue] 癌症研究 85卷 12期 https://aacrjournals.org/cancerres/issue/ In the Spotlight（焦点） 1 Incorporating Centrally Tolerized Mice as a Design Principle to Circumvent Reporter Immunogenicity in Cancer Research Models 将中央耐受小鼠作为设计原则以规避癌症研究模型中报告基因的免疫原性 Candice A. Grzelak; Cyrus M. Ghajar Cancer Res (2025) 85 (12): 2143–2145. 2 To EMT or Not to EMT: Ablation of Mesenchymal Tumor Cell Lineages Reveals the Essential Role of EMT in Pancreatic Cancer Initiation and Evolution 上皮-间质转化（EMT）之惑：间质肿瘤细胞谱系消融揭示EMT在胰腺癌起始和演变中的关键作用 Jessica Peura; Calvin Johnson; Jason R. Pitarresi Cancer Res (2025) 85 (12): 2146–2148. 3 Hotspots of Escape: Oxidative Niches Prime Tumor Cell Dissemination 逃逸热点：氧化微环境促使肿瘤细胞扩散 Mario Palma; Marie Sabatier; Jessalyn M. Ubellacker Cancer Res (2025) 85 (12): 2149–2151. Review（综述） 4 Transforming Cancer Therapy: Unlocking the Potential of Targeting Vascular and Stromal Cells in the Tumor Microenvironment 癌症治疗变革：解锁靶向肿瘤微环境中血管和基质细胞的潜力 Lu Liu; Yuheng Zhang; Hanyu Liu; Jian Yang; Qi Tian; Nareekarn Chueakula; Saravana Ramasamy; Navin Kumar Verma; Christine Cheung; Anjali P. Kusumbe Cancer Res (2025) 85 (12): 2152–2164. Cancer Biology（癌症生物学） 5 Immunological Tolerance to Luciferase and Fluorescent Proteins Using Tol Mice Enables Development of Improved Tumor Models for Investigating Immunity and Metastasis 利用Tol小鼠对荧光素酶和荧光蛋白产生免疫耐受，助力开发用于研究免疫和转移的改进型肿瘤模型 Kabir A. Khan; Areeba A. Qureshi; Ping Xu; Hung-Yang Kuo; Ton N. Schumacher; Iacovos P. Michael; Robert S. Kerbel Cancer Res (2025) 85 (12): 2165–2178. 6 Targeting the Dependence on PIK3C3-mTORC1 Signaling in Dormancy-Prone Breast Cancer Cells Blunts Metastasis Initiation 靶向休眠倾向乳腺癌细胞对PIK3C3-mTORC1信号通路的依赖性，抑制转移起始 Islam E. Elkholi; Amélie Robert; Camille Malouf; Joshua L. Wu; Hellen Kuasne; Stanislav Drapela; Graham Macleod; Steven Hébert; Alain Pacis; Virginie Calderon; Claudia L. Kleinman; Ana P. Gomes; James V. Alvarez; Julio A. Aguirre-Ghiso; Morag Park; Stéphane Angers; Jean-François Côté Cancer Res (2025) 85 (12): 2179–2198. 7 Cancer-Associated Fibroblasts Foster a High-Lactate Microenvironment to Drive Perineural Invasion in Pancreatic Cancer 癌症相关成纤维细胞营造高乳酸微环境，推动胰腺癌神经周围浸润 Tingting Li; Chonghui Hu; Tianhao Huang; Yu Zhou; Qing Tian; Huimou Chen; Rihua He; Yuan Yuan; Yong Jiang; Honghui Jiang; Kaijun Huang; Di Cheng; Rufu Chen; Shangyou Zheng Cancer Res (2025) 85 (12): 2199–2217. Cancer Immunology（癌症免疫学） 8 Age-Associated Modulation of TREM1/2-Expressing Macrophages Promotes Melanoma Progression and Metastasis 年龄相关调节表达TREM1/2的巨噬细胞，促进黑色素瘤进展和转移 Marzia Scortegagna; Rabi Murad; Parinaz Bina; Yongmei Feng; Rebecca A. Porritt; Alexey V. Terskikh; Xiao Tian; Peter D. Adams; Kristiina Vuori; Ze’ev A. Ronai Cancer Res (2025) 85 (12): 2218–2233. 9 Targeting PRC2 Enhances the Cytotoxic Capacity of Anti-CD19 CAR T Cells against Hematologic Malignancies 靶向PRC2可增强抗CD19嵌合抗原受体（CAR）T细胞对血液系统恶性肿瘤的细胞毒能力 Maria Leticia Rodrigues Carvalho; Clara de Oliveira Andrade; Mariela Pires Cabral-Piccin; Gabriela Sarti Kinker; Glauco Akelinghton Freire Vitiello; Raylane Adrielle Gonçalves Cambuí; Luiza de Macedo Abdo; Eduardo Mannarino Correia; Bruno Dalbelo da Silva Elias; Emmanuel Vinicius Oliveira Araujo; Alexandre Silva Chaves; Pedro Henrique Barbosa Pereira; Karina Lobo Hajdu; Amanda Rondinelli; Arianne Fagotti Gusmão; Maria Luisa Marques Pierre; Igor Brasil-Costa; Caroline Pouza Zanella; Marta Maria Moreira Lemos; Marjorie Vieira Batista; Jayr Schmidt Filho; Cheryl Arrowsmith; Vladmir Cláudio Cordeiro de Lima; Martin Hernán Bonamino; Tiago da Silva Medina Cancer Res (2025) 85 (12): 2234–2249. 10 SLC3A2-Mediated Lysine Uptake by Cancer Cells Restricts T-cell Activity in Hepatocellular Carcinoma 癌细胞通过SLC3A2介导的赖氨酸摄取限制肝细胞癌中的T细胞活性 Yating Chang; Naizhen Wang; Shaopeng Li; Jiaqi Zhang; Yipeng Rao; Zilong Xu; Lu Li; Hongning Wu; Jun Chen; Yanhua Lin; Xiaoxuan Huang; Pingguo Liu; Jun Zhang; Yueting Liao; Chaolong Lin; Chenghao Huang; Ningshao Xia Cancer Res (2025) 85 (12): 2250–2267. Translational Cancer Biology（癌症转化生物学） 11 Blocking Nitrosylation Induces Immunogenic Cell Death by Sensitizing NRAS-Mutant Melanoma to MEK Inhibitors 阻断亚硝基化通过使NRAS突变型黑色素瘤对MEK抑制剂敏感而诱导免疫原性细胞死亡 Jyoti Srivastava; Vipin K. Yadav; Rachel V. Jimenez; Pravin R. Phadatare; Ninad A. Inamdar; Montana M. Young; Antonella Bacchiocchi; Ruth Halaban; Bin Fang; Alvaro de Mingo Pulido; Kenneth Y. Tsai; Keiran S.M. Smalley; John M. Koomen; Paulo C. Rodriguez; Sanjay Premi Cancer Res (2025) 85 (12): 2268–2287. 12 A Genome-Wide Synthetic Lethal Screen Identifies Spermidine Synthase as a Target to Enhance Erdafitinib Efficacy in FGFR-Mutant Bladder Cancer 全基因组合成致死筛选确定精脒合成酶为增强厄达替尼在FGFR突变型膀胱癌中疗效的靶点 Yanchao Yu; Xincheng Gao; Huayuan Zhao; Jiayin Sun; Miao Wang; Xing Xiong; Junping Li; Chao Huang; Hui Zhang; Guosong Jiang; Xingyuan Xiao Cancer Res (2025) 85 (12): 2288–2301. 13 Single-Cell Expression Analysis of Ductal Carcinoma In Situ Identifies Complex Genotypic–Phenotypic Relationships Altering Epithelial Composition 导管原位癌的单细胞表达分析确定了改变上皮成分的复杂基因型-表型关系 Xiaodi Qin; Siri H. Strand; Marissa R. Lee; Aashrith Saraswathibhatla; David G.P. van IJzendoorn; ChunFang Zhu; Sujay Vennam; Sushama Varma; Allison Hall; Rachel E. Factor; Lorraine King; Lunden Simpson; Xiaoke Luo; Graham A. Colditz; Shu Jiang; Ovijit Chaudhuri; E. Shelley Hwang; Jeffrey R. Marks; Kouros Owzar; Robert B. West Cancer Res (2025) 85 (12): 2302–2319. Cancer Landscapes（癌症特征） 14 Spatial Profiling Identifies Regionally Distinct Microenvironments and Targetable Immunosuppressive Mechanisms in Pediatric Osteosarcoma Pulmonary Metastases 空间分析确定儿童骨肉瘤肺转移的区域特异性微环境和可靶向的免疫抑制机制 Jason Eigenbrood; Nathan Wong; Paul Mallory; Janice S. Pereira; Demond Williams; Douglass W. Morris-II; Jessica A. Beck; James C. Cronk; Carly M. Sayers; Monica Mendez; Linus Kaiser; Julie Galindo; Jatinder Singh; Ashley Cardamone; Milind Pore; Michael Kelly; Amy K. LeBlanc; Jennifer Cotter; Rosandra N. Kaplan; Troy A. McEachron Cancer Res (2025) 85 (12): 2320–2337. Editor’s Notes（编者按） 15 Editor’s Note: Inverse Correlation of STAT3 and MEK Signaling Mediates Resistance to RAS Pathway Inhibition in Pancreatic Cancer 编者按：STAT3和MEK信号通路的负相关介导胰腺癌对RAS通路抑制的耐药性 Nagaraj S. Nagathihalli; Jason A. Castellanos; Purushottam Lamichhane; Fanuel Messaggio; Chanjuan Shi; Xizi Dai; Priyamvada Rai; Xi Chen; Michael N. VanSaun; Nipun B. Merchant Cancer Res (2025) 85 (12): 2338. 16 Editor’s Note: Lactate Dehydrogenase B Is Critical for Hyperactive mTOR-Mediated Tumorigenesis 编者按：乳酸脱氢酶B对mTOR过度激活介导的肿瘤发生至关重要 Xiaojun Zha; Fang Wang; Ying Wang; Shaozong He; Yanling Jing; Xueyan Wu; Hongbing Zhang Cancer Res (2025) 85 (12): 2339. 17 Editor’s Note: Recombinant Immunoproapoptotic Proteins with Furin Site Can Translocate and Kill HER2-Positive Cancer Cells 编者按：带有弗林蛋白酶位点的重组免疫促凋亡蛋白可转位并杀伤HER2阳性癌细胞 Tao Wang; Jing Zhao; Jun-Lin Ren; Li Zhang; Wei-Hong Wen; Rui Zhang; Wei-Wei Qin; Lin-Tao Jia; Li-Bo Yao; Ying-Qi Zhang; Si-Yi Chen; An-Gang Yang Cancer Res (2025) 85 (12): 2340.

现有的PAH疗法 | 靶向治疗 对于急性血管扩张试验未显示即时血流动力学改善，或对大剂量钙通道阻滞剂治疗无持续反应的PAH患者，推荐采用针对前列环素、内皮素或一氧化氮途径的疗法。美国或欧洲批准的靶向PAH疗法关键试验的主要结局总结如下。 前列环素类似物：在一项针对PAH患者（NYHA心功能III-IV级）的随机、对照、开放标签12周研究中评估了前列环素类似物依前列醇。这项关键研究表明，与常规治疗相比，静脉注射依前列醇改善了运动耐力（6分钟步行距离）和血流动力学测量指标。该研究仍是迄今为止唯一显示试验新药相比标准治疗能提高生存率的PAH试验。但需注意，该研究中的常规背景治疗（包括抗凝药、口服血管扩张剂、利尿剂、强心苷和辅助供氧）与后续研究（其中患者可能已接受其他既定PAH治疗作为背景治疗）不同，且所有患者均属晚期疾病。 后续获批的前列环素类似物旨在具有更佳的安全性特征和更便捷的给药途径。评估皮下曲前列尼尔、吸入伊洛前列素、吸入曲前列尼尔和口服曲前列尼尔的关键试验表明，与安慰剂相比，治疗12周后6分钟步行距离均有改善。静脉曲前列尼尔在健康志愿者中显示出与皮下曲前列尼尔的生物等效性，当无法耐受皮下曲前列尼尔输注时可考虑使用。此外，口服前列环素受体激动剂司来帕格，无论背景治疗如何，相比安慰剂降低了死亡与PAH所致并发症复合事件的发生率。主要终点事件中大部分（81.9%）为住院或疾病进展。 内皮素受体拮抗剂：同样，评估口服内皮素受体拮抗剂（ERAs）波生坦和安立生坦的关键试验表明，在未经治疗的PAH患者中，与安慰剂相比，分别治疗16周和12周后6分钟步行距离（6MWD）均有改善（表1）。随后一项评估马西替坦的试验，针对已接受至多两种PAH特异性背景治疗的患者，结果显示该药相比安慰剂降低了发病率和死亡率复合事件的发生率。 靶向一氧化氮通路：一氧化氮刺激可溶性鸟苷酸环化酶（sGC）生成环磷酸鸟苷，后者可被磷酸二酯酶5（PDE5）降解。在未经治疗的PAH患者中，口服PDE5抑制剂西地那非和他达拉非在分别治疗12周和16周后，与安慰剂相比均改善了6MWD。类似地，在接受ERAs或前列腺素类药物治疗或未接受其他PAH特异性治疗的有症状PAH患者中，sGC刺激剂利奥西呱在治疗12周后相比安慰剂改善了6MWD。 表1 | 已完成的已发表肺动脉高压III期临床试验 6MWD，6分钟步行距离；CTD-PAH，结缔组织病相关肺动脉高压；ERA，内皮素受体拮抗剂；IV，静脉注射；NYHA，纽约心脏病协会；PAH，肺动脉高压；PDE5，磷酸二酯酶5；PH，肺动脉高压；RCT，随机对照试验；SC，皮下注射。 | 初始联合治疗 III–IV期AMBITION试验在新诊断的PAH患者（WHO功能分级II级和III级）中，比较了初始安立生坦或他达拉非单药治疗与初始安立生坦联合他达拉非联合治疗的疗效。初始联合治疗方案显著降低了临床失败复合终点的风险，优于单药治疗。 值得注意的是，该研究首次采用了扩展定义的"至临床失败时间"事件驱动复合终点，其中功能分级"无改善"合并步行距离任何恶化即被视为治疗"失败"。然而，两个治疗组在复合终点发生率上的差异主要由因PAH住院所驱动。前期联合治疗的这一额外获益是源于两类药物机制上的协同作用，还是每类药物部分补偿了对另一类药物无反应的情况，仍有待确定。 一项法国注册登记研究显示，接受ERA和PDE5抑制剂双药联合治疗的新诊断PAH患者，在4个月后WHO功能分级、运动耐量和血流动力学指标均有改善。此外，两项临床试验的结果表明，接受ERA和PDE5抑制剂双药口服联合治疗但未达到预设临床疗效标准的患者，可能受益于从PDE5抑制剂转换为利奥西呱。然而，鉴于这两项试验均为开放标签研究，需要盲法对照研究来证实这些发现。 最后，TRITON研究显示，在新诊断、未接受过治疗的PAH患者中，三联联合治疗（马西替坦、他达拉非和司来帕格）与双联联合治疗（马西替坦和他达拉非）在主要终点PVR方面无显著差异。最新的欧洲肺动脉高压治疗指南推荐，对于无心肺合并症的PAH患者（特发性、遗传性、药物相关或结缔组织病相关）采用初始联合治疗，而对于伴有心肺合并症的患者则采用初始口服单药治疗。 重要的是，PAH药物只有在患者能够耐受其剂量、给药途径和不良反应特征时才有效。一种药物的治疗前景可能会影响患者应对不良反应的能力或意愿。例如，对于具有挽救生命潜力和疾病修饰特性的药物，相比疗效较差的药物，其不利的副作用特征将更容易被接受。 值得注意的是，同类药物中的不同药物可能具有不同的副作用。一项比较多种ERA临床安全性的荟萃分析显示，波生坦治疗会增加肝功能异常的风险，而安立生坦或马西替坦治疗则无此风险。关于前列环素疗法，随着皮下、口服和吸入制剂的发展，静脉治疗相关的并发症和负担将得以减轻。然而，联合治疗将伴随每种药物不良反应的累积，这可能会影响耐受性（图2）。 图2 | 已获批及处于研发后期的肺动脉高压疗法的主要不良反应概览 联合治疗将伴随各类药物不良反应的累积效应。CNS，中枢神经系统；ERAs，内皮素受体拮抗剂；GERD，胃食管反流病；PDE5，磷酸二酯酶5。 | 钙通道阻滞剂 对于急性血管反应试验呈阳性的特发性、遗传性或药物相关性PAH患者，可能受益于大剂量钙通道阻滞剂治疗。然而，这些患者对钙通道阻滞剂的初始疗效往往无法长期维持。 一项法国全国注册登记研究显示，12.6%的特发性PAH患者对急性血管扩张试验有急性血流动力学反应，但仅6.8%的患者在治疗1年后对钙通道阻滞剂保持持续反应。在一项针对1904例接受血管反应性测试的特发性、遗传性或药物诱导性PAH患者的多中心回顾性分析中，仅162例患者符合血管反应者标准。在中位60个月的随访期间，总生存率为86.7%。但在开始钙通道阻滞剂治疗1年后，仅53.2%的患者仍维持该方案的单药治疗。 值得注意的是，除先前定义的血液动力学反应者标准外，该研究还显示初始血管反应性测试期间的肺动脉顺应性、低风险状态以及随访期间较低的血清NT-proBNP水平与生存率相关。因此，对血管扩张剂挑战试验呈阳性反应并处方钙通道阻滞剂的患者，应定期通过客观检测进行再评估。需要指出的是，在所有PAH治疗中，鉴于能够预先识别可能的应答者，钙通道阻滞剂治疗仍是目前唯一可用的"个体化医疗"工具。 | 现有疗法的局限性 肺动脉高压（PAH）复杂的血管病理生物学特征，包括肺血管细胞过度增殖、细胞外基质沉积及血管周围炎症细胞浸润，对现有治疗方法构成了挑战。 现有的PAH疗法其作用机制主要局限于通过纠正血管活性因子失衡来实现血管舒张作用。 评估这些疗法的临床试验主要聚焦于基于6分钟步行距离（6MWD）或由疾病进展及住院驱动的发病率与死亡率终点来判断其获益（表1）；迄今为止，尚无临床试验能够证明哪种药物组合对个体患者最为理想，或能提供疾病修饰的确凿证据。 因此，医生缺乏证据来预测哪种药物或药物组合对特定患者最有效。目前尚缺乏能够预先识别可能应答者的个体化医疗方法（例如像使用钙通道阻滞剂时那样），但"大数据"和组学工具未来或有助于弥补这一证据缺口（见下文）。 此外，需要新的策略来解决肺部病理性重塑，并阻止或逆转PAH的进展。过去数十年的转化与临床研究已揭示了导致PAH增殖、代谢和炎症异常的新型致病通路，为新的治疗途径提供了见解。 新型治疗靶点 | 伊马替尼 酪氨酸激酶抑制剂伊马替尼是该类药物中首个在PAH患者中进行测试的药物，为研究具有显著抗增殖特性（相对于血管舒张特性）的新型药物以逆转血管病理学开启了大门。 伊马替尼是多种酪氨酸激酶的选择性抑制剂，包括融合蛋白BCR–ABL（促进白细胞增殖）、KIT及血小板衍生生长因子受体（PDGFR）（图3）。 伊马替尼于2001年被批准用于治疗慢性髓系白血病患者。PDGF已被证明是平滑肌细胞和成纤维细胞的强效促有丝分裂剂和趋化剂，并能强效诱导平滑肌收缩活性；而KIT是骨髓来源的造血干细胞的标志物。鉴于肺血管重塑与PAH患者PDGF活性上调和KIT表达增加相关，重新利用伊马替尼治疗PAH的潜力备受关注。 在已确立肺血管疾病的动物模型中，伊马替尼治疗与小肺动脉的显著"反向重塑"效应相关，这与其抗增殖特性一致。随后的病例报告显示，对一例尽管接受三联治疗仍进展至右心衰竭的终末期PAH患者给予口服伊马替尼，改善了其6分钟步行距离、肺血管阻力和WHO功能分级。这些效应在治疗6个月后得以维持，且无明显不良反应。 在数篇类似病例报告发表后，一项在PAH患者中开展的为期24周的II期随机对照研究显示，与安慰剂相比，伊马替尼治疗后肺血管阻力显著降低，6分钟步行距离有所增加（尽管不显著）。随后的III期IMPRES试验表明，在常规PAH治疗基础上加用伊马替尼的患者，与接受安慰剂加常规PAH治疗的患者相比，6分钟步行距离、肺血管阻力和心输出量均有显著改善（表1）。 然而，不良事件（如硬膜下血肿）和研究药物停药在伊马替尼组比安慰剂组更常见，且FDA已要求进一步的安全性数据。 尽管如此，伊马替尼用于PAH治疗仍引起相当大兴趣。一项I期试验显示，干粉吸入制剂伊马替尼（AV-101）在健康志愿者中耐受性良好，且与口服伊马替尼相比全身暴露量减少。一项在PAH患者中正在进行的II–III期试验将评估AV-101对比安慰剂的安全性和有效性，其II期部分的主要终点为24周时肺血管阻力的变化，III期部分的主要终点为24周内6分钟步行距离的变化。 此外，一项开放标签、单臂、I–II期临床研究正在进行中，旨在确定PAH患者口服伊马替尼的最佳耐受剂量，评估该剂量下的疗效，并依据患者基因型评价药物反应。 | Seralutinib 酪氨酸激酶抑制剂Seralutinib通过吸入给药，靶向PDGFRα、PDGFRβ、集落刺激因子1受体和KIT（图3）。在两种PAH啮齿动物模型中，与载体治疗相比，吸入Seralutinib改善了心肺血流动力学，并减轻了肺动脉和右心室重塑。在接受标准背景治疗的PAH患者中开展的II期随机双盲安慰剂对照TORREY试验显示，在24周时，吸入Seralutinib与安慰剂相比显著降低了肺血管阻力，达到了研究的主要终点。Seralutinib耐受性良好，两组中最常见的不良事件为轻度至中度咳嗽。这些结果表明，通过吸入给药可使药物在肺循环中具有足够活性，且安全性良好。一项在PAH患者中正在进行的III期试验将评估吸入Seralutinib对比安慰剂的安全性和有效性，主要终点为24周内6分钟步行距离的变化。 图3 | 肺血管疾病中针对新靶点的关键研究性治疗方案 1）酪氨酸激酶抑制剂伊马替尼是首个主要在非血管舒张方面对肺动脉高压（PAH）患者进行测试的药物。伊马替尼和另一种酪氨酸激酶抑制剂Seralutinib的吸入制剂正在II期和III期临床试验中进行评估。 2）激活素受体IIA型（ACTRIIA）配体陷阱Sotatercept于2024年在美国获批使用；针对PAH患者的ACTRIIB配体陷阱KER-012的II期试验正在进行中。 3）性激素相关疗法（阿那曲唑、他莫昔芬和脱氢表雄酮（DHEA））以及靶向代谢的药物（二甲双胍和曲美他嗪）也在研究中。 4）重组骨形态发生蛋白9（BMP9）也正在被开发为PAH的潜在治疗方法，尽管BMP9在PAH中的作用仍未明确。 ALK，激活素受体样激酶；BMPR，骨形态发生蛋白受体；CoA，辅酶A；CSF1R，集落刺激因子1受体；DCA，二氯乙酸；EndMT，内皮-间质转化；ER，雌激素受体；GDFs，生长和分化因子；ID，DNA结合蛋白抑制剂ID；IL-6R，IL-6受体；NF-κB，核因子-κB；NFAT，活化T细胞核因子；PDGFR，PDGF受体；PDH，丙酮酸脱氢酶；ROS，活性氧；TCA，三羧酸；VEGF，血管内皮生长因子。 | Sotatercept Sotatercept是一种首创的融合蛋白，由人激活素受体IIA型（ACTRIIA）胞外结构域和人免疫球蛋白G1的Fc结构域组成。Sotatercept作为一种配体陷阱，通过隔离TGFβ超家族成员，恢复促增殖的ACTRIIA通路与抗增殖的BMPR2通路之间的平衡（图3）。 PAH患者肺小动脉中ACTRIIA配体激活素、生长分化因子8（GDF8）和GDF11的表达高于健康对照。临床前研究中，ACTRIIA–Fc融合蛋白能促进BMP9信号传导，并阻断GDF11和激活素在肺血管细胞中的促增殖效应。该融合蛋白还在两种肺动脉高压啮齿动物模型中预防并逆转了肺血管疾病和右心室功能障碍。 在一项II期随机安慰剂对照试验中，对于接受稳定背景治疗的PAH患者，皮下注射Sotatercept在24周时相比安慰剂显著降低了肺血管阻力。Sotatercept治疗带来的肺血管阻力降低主要是由平均肺动脉压下降驱动，因为心输出量变化极小。 在该试验的开放标签、18–24个月延长期中，所有参与者均接受Sotatercept治疗，结果显示从延长期开始时由安慰剂转为Sotatercept的患者其疗效终点得到改善，而原Sotatercept组的疗效得以维持。最后，在一项III期随机试验中，将皮下注射Sotatercept与安慰剂在接受稳定背景治疗的PAH患者中进行比较（表1）。 大多数患者（61.6%）接受了背景三联治疗。与安慰剂组相比，Sotatercept组在主要终点6分钟步行距离上显示出显著改善，同时在次要终点（包括肺血管阻力、血浆NT-proBNP水平、WHO功能分级、至死亡或临床恶化的时间、法国风险评分以及患者报告结局）上也均有显著改善。与II期试验一致，心输出量观察到的变化极小。 尽管疗效数据令人印象深刻，但新出现的安全性信号值得讨论。在II期试验中，Sotatercept组出现血小板减少和血红蛋白水平升高，而安慰剂组未见此现象，这与预期一致。在II期试验的长期延长期中，也有11名参与者（10.6%）报告毛细血管扩张作为不良事件。在III期试验中，Sotatercept治疗组相比安慰剂组更频繁发生轻微出血事件、鼻衄、牙龈出血、头晕和血压升高。 尽管在接受Sotatercept治疗的患者中尚未报告危险的动静脉畸形，但毛细血管扩张的报告提示存在脱靶的全身血管效应，需要进一步研究。 值得注意的是，ALK1基因变异与伴有遗传性出血性毛细血管扩张症的PAH相关。接受Sotatercept治疗的患者在心输出量上缺乏有益变化，尽管肺血管阻力和平均肺动脉压有所改善，这一现象也出乎意料，且可能令人担忧，因为临床前数据提示Sotatercept类药物可能对心脏产生不利影响。 然而，需注意研究参与者均接受了既定的PAH治疗，且基线时心指数正常，这可能部分解释了心指数未能进一步增加的原因。这些安全性发现的长期影响仍有待确定。 一项在PAH患者中进行的开放标签随访研究正在进行，以评估Sotatercept的长期安全性、耐受性和疗效。此外，另外两项III期试验目前正在评估Sotatercept用于死亡高风险PAH患者（WHO功能分级III或IV级）以及新诊断的疾病进展中高风险PAH患者。 | 重组BMP9 BMP9的基因变异与PAH相关，且部分患者即使不存在这些变异，其BMP9表达也会降低。MGX292是一种重组BMP9变体，与天然BMP9相比，其成骨活性降低而内皮信号活性相似；该药物在严重闭塞性PAH大鼠模型中逆转了肺血管重塑，目前正被开发为PAH的潜在疗法。 然而，BMP9作为PAH治疗靶点的作用存在争议。 研究表明，在严重闭塞性PAH啮齿类动物模型中，给予BMP9可逆转肺血管疾病；在伴有肺纤维化的肺血管疾病啮齿类动物模型中，BMP9能减轻肺血管疾病特征。但相反的是，其他研究显示删除或抑制BMP9可减轻肺血管疾病。 这些发现可通过以下现象解释：编码BMP9受体ALK1和共受体内皮糖蛋白的基因变异与遗传性出血性毛细血管扩张症相关；删除或抑制BMP9可能导致血管舒张，类似于出血性毛细血管扩张症中所见，这可能对肺血管疾病的发展起到保护作用。 更复杂的是，小鼠中细胞类型特异性的BMP9和BMP10基因失活可减弱血管平滑肌细胞收缩性并降低血压；相反，BMP10的过表达则增加血管收缩性和血压。总体而言，鉴于临床前和临床数据的矛盾，BMP9在PAH中的作用仍未明确。 | 性激素相关疗法 肺动脉高压动物模型的研究报告了雌二醇对肺血管系统的不一致效应，但该激素显示出对右心室功能及适应具有保护作用。在两种肺动脉高压啮齿类动物模型中，使用芳香酶抑制剂阿那曲唑抑制雌二醇合成可减轻肺血管疾病的发展，但仅对雌性啮齿动物有效。 在一项针对接受稳定背景治疗的男性和绝经后女性PAH患者的小型原理验证随机对照试验中，与安慰剂相比，阿那曲唑耐受性良好并增加了6分钟步行距离，尽管在右心室参数（通过超声心动图评估）、循环生物标志物、功能分级或健康相关生活质量方面未观察到改善。目前正在等待一项针对类似患者群体的更大规模随机对照II期试验的结果。 他莫昔芬（一种雌激素受体拮抗剂）在PAH中的作用也已被探索。在遗传性PAH（携带Bmpr2突变的小鼠）的临床前模型中，他莫昔芬部分逆转了肺血管疾病。尽管在小鼠模型中，联合使用阿那曲唑和氟维司群以更強效地抑制雌激素似乎对PAH治疗更有效，但考虑到诱导绝经的风险较低，他莫昔芬可能对绝经前女性PAH患者更有用。一项评估他莫昔芬用于接受稳定背景治疗的男性和女性（包括绝经前和绝经后）PAH患者的小型随机对照II期临床试验结果尚待公布。 最后，脱氢表雄酮（DHEA）作为雌激素和睾酮的前体，已被证明能在严重闭塞性PAH大鼠模型及其他形式的肺血管疾病模型中减轻肺血管重塑。一项评估DHEA对慢性阻塞性肺疾病相关肺动脉高压患者疗效的非对照初步试验显示，DHEA治疗与6分钟步行距离和肺血流动力学指标较基线改善相关，且无气体交换恶化的证据。一项评估DHEA对接受稳定背景治疗的PAH患者影响的II期试验正在进行中。 | 代谢调节疗法 肺动脉高压与代谢功能障碍相关，而抗糖尿病药物二甲双胍已被证明对PAH具有保护作用，这可能归因于其血管舒张和抗增殖特性。在低氧或野百合碱诱导的肺动脉高压大鼠模型中，二甲双胍能够防止肺血管重塑；但在低氧联合VEGF受体抑制剂SU5416诱导的严重闭塞性PAH模型中，该保护作用仅见于雌性大鼠。 一项随机对照初步试验显示，在先天性心脏病相关PAH患者中，二甲双胍与波生坦联合治疗在改善6分钟步行距离和肺血管阻力指数方面优于波生坦单药治疗。目前一项II期随机对照试验正在评估二甲双胍对接受稳定背景治疗的PAH患者的疗效。 靶向Warburg效应（即在有氧条件下细胞代谢从葡萄糖氧化转向糖酵解）也是PAH治疗的一个方向。二氯乙酸通过抑制丙酮酸脱氢酶激酶促进葡萄糖氧化（图3）。 在肺血管疾病啮齿类模型中，二氯乙酸通过恢复电压门控钾通道的表达和功能、减少肺动脉细胞增殖并促进细胞凋亡，从而预防并逆转了疾病。其右心室功能改善既源于肺血管疾病的消退，也来自二氯乙酸对右心室的直接作用。 在严重闭塞性PAH大鼠模型中，二氯乙酸能预防但未能逆转新生内膜病变的形成。接受二氯乙酸开放标签治疗4个月的特发性PAH患者，其平均肺动脉压、肺血管阻力和功能能力总体较基线改善，但携带Sirtuin 3和解偶联蛋白2功能缺失多态性的亚组患者无治疗反应，且接受最高剂量患者出现了剂量限制性毒性（2级周围神经病变）。 考虑到这种剂量限制性的神经病变风险及个体间药物代谢的显著差异，二氯乙酸可能并非PAH的理想治疗候选药物。然而这些研究发现证明了靶向PAH细胞代谢改变的可行性及个体化治疗的重要性。 葡萄糖氧化也可能通过使用脂肪酸氧化抑制剂（如曲美他嗪）激活Randle循环而间接促进。在肺动脉束带大鼠中，与安慰剂相比，曲美他嗪预防了右心室肥厚的发展，并改善了心指数和运动能力。一项针对PAH患者的II期随机对照初步试验显示，与安慰剂相比，曲美他嗪虽改善幅度较小但显著改善了右心室重塑，并显著增加了6分钟步行距离。 | 5-羟色胺通路 PAH患者血浆5-羟色胺水平较健康志愿者升高，且芬氟拉明等食欲抑制剂（可增加5-羟色胺可用性）与PAH风险增加相关。然而，疾病中发生改变的信号通路未必是其治疗的合适靶点。 多种靶向5-羟色胺通路的药物（包括受体拮抗剂、受体激动剂和转运体再摄取抑制剂）曾作为PAH潜在疗法被研究，但均在临床试验中未获成功。一项针对色氨酸羟化酶抑制剂rodatristat ethyl（靶向5-羟色胺生物合成）的IIb期研究未达到24周时肺血管阻力变化的主要终点。基于这些早期研究结果（包括安全性数据分析），该药物的后续研究已终止。 参考文献：https://doi.org/10.1038/s41569-024-01064-4 声明：本文只供生命科学、医学、药学等相关专业人士学习交流之用，不作为任何就医用药指导，如有不适请及时就医。 相关阅读：肺动脉高压（PAH）的发病机制与治疗：病理生理学 慢性阻塞性肺病（COPD）：药物靶点与新药研发管线