Zanzalintinib

Issued on behalf of GT Biopharma, Inc. USA News Group News Commentary VANCOUVER, BC, Dec. 4, 2025 /PRNewswire/ -- Triple-therapy immunotherapy approaches are demonstrating complete leukemia elimination in preclinical models by reprogramming how cancer cells die to trigger powerful immune responses[1], while breakthrough natural killer cell research is revealing new pathways to supercharge the body's innate tumor-fighting capabilities[2]. These developments position GT Biopharma, Inc. (NASDAQ: GTBP), Geron Corporation (NASDAQ: GERN), Kura Oncology, Inc. (NASDAQ: KURA), SELLAS Life Sciences Group, Inc. (NASDAQ: SLS), and TScan Therapeutics, Inc. (NASDAQ: TCRX). The FDA's November approval of the first once-daily menin inhibitor for relapsed NPM1-mutated AML[3] validates targeted blood cancer therapies as investors and institutions recognize timing advantages before late-stage clinical catalysts materialize across the competitive landscape. GT Biopharma, Inc. (NASDAQ: GTBP) recently announced successful completion of the formal safety review for its ongoing Phase 1 clinical trial of GTB-3650's third dosing group (Cohort 3), with no safety or tolerability issues observed. With all the significant recent progress of GTB-3650, GTBP is currently advancing innovative immunotherapy treatments designed to combat some of the world's most challenging cancer types. This latest milestone has allowed GT Biopharma to advance into Cohort 4, where patients will receive 10μg/kg/day. Now the company is actively screening patients for Cohort 4 and anticipates initiating dosing in the coming weeks, with the next comprehensive update expected in the first quarter of 2026. The Phase 1 study is testing GTB-3650 in patients battling relapsed or refractory blood cancers that express the CD33 protein, specifically acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). These represent some of the most difficult cancer cases to treat, involving patients whose disease either came back after initial therapy or never responded to conventional treatment options. GTB-3650 works by stimulating the patient's natural killer cells, a type of immune cell that naturally hunts down and destroys abnormal cells, to specifically target cancer cells. Patients receive the therapy through continuous infusions following a structured schedule: two weeks of treatment followed by two weeks of rest, repeating this cycle for up to four months based on how they respond. The six patients enrolled across Cohorts 1 through 3 have all been successfully treated with GTB-3650, demonstrating the therapy's tolerability at progressively higher dose levels. According to the company, the Cohort 4 dose level of 10μg/kg/day is more reflective of the potential clinical efficacy threshold. This assessment is based on positive trends observed across multiple immunological biomarkers from the previous six patients, the complete absence of dose-limiting toxicities throughout all three completed cohorts, and recognition that the earlier cohorts utilized lower dose levels that may have been below the therapeutic range where meaningful clinical benefit occurs. The Phase 1 design calls for testing GTB-3650 in approximately 14 patients across seven cohorts, with two patients per cohort receiving progressively higher doses from 1.25μg/kg/day in Cohort 1 up to 100μg/kg/day in Cohort 7 if necessary. Beyond the current Cohort 4, three additional higher-dose cohorts remain available: Cohort 5 at 25μg/kg/day, Cohort 6 at 50μg/kg/day, and Cohort 7 at the maximum planned dose of 100μg/kg/day. This wide dosing range reflects the trial's goal of identifying where GTB-3650 delivers optimal therapeutic benefit while maintaining an acceptable safety profile. The trial is measuring safety, pharmacokinetics, pharmacodynamics, in vivo expansion of endogenous patient natural killer cells, and clinical activity. Beyond blood cancers, the company is developing GTB-5550, which targets B7H3, a protein commonly found across various solid tumor types including breast, lung, ovarian, pancreatic, bladder, and prostate cancers. GT Biopharma plans to file its regulatory application to begin human trials of GTB-5550 either in the fourth quarter of 2025 or in January 2026. GTB-5550 is being designed as a subcutaneous injection that patients might eventually self-administer at home. Both candidates utilize GT Biopharma's proprietary TriKE platform technology, which employs specialized antibody fragments originally found in camels and llamas. These molecules offer advantages over conventional antibodies due to their smaller size and greater stability. The company holds an exclusive worldwide license from the University of Minnesota for this technology. CONTINUED… Read this and more news for GT Biopharma, Inc. at: Geron Corporation (NASDAQ: GERN) achieved $47.2 million in RYTELO net product revenue in the third quarter of 2025 and completed enrollment of 320 patients in its Phase 3 IMpactMF clinical trial evaluating imetelstat in relapsed/refractory myelofibrosis. The commercial-stage biopharmaceutical company strengthened its leadership team with the appointment of Ahmed ElNawawi as Chief Commercial Officer and now has approximately 1,150 ordering accounts for RYTELO, an increase of approximately 150 quarter-over-quarter. "The high unmet need in lower-risk MDS is well known, and RYTELO is a therapy with a novel mechanism of action and the potential to significantly impact the treatment paradigm," said Harout Semerjian, President and CEO of Geron. " Geron is positioned, with our realigned leadership team, to strengthen commercial execution, increase both physician and patient awareness, and drive RYTELO sales in the U.S." Geron expects the IMpactMF interim analysis readout for overall survival in the second half of 2026 and final analysis in the second half of 2028. The company reduced its 2025 total operating expenses guidance to between $250 million and $260 million from the previously announced $270 million to $285 million, with cash, cash equivalents, restricted cash and marketable securities of approximately $421.5 million as of September 30, 2025. Kura Oncology, Inc. (NASDAQ: KURA) announced that KOMZIFTI (ziftomenib), the first and only once-daily FDA-approved menin inhibitor for adults with relapsed or refractory acute myeloid leukemia with a susceptible NPM1 mutation, has been included in the NCCN Guidelines as a Category 2A recommended treatment option. The drug received full FDA approval on November 13, 2025, supported by data from the KOMET-001 clinical trial demonstrating a 21.4% complete response rate and median duration of response of 5 months, and is now commercially available to prescribers in the U.S. through a limited network of specialty pharmacies and distributors. "The addition of KOMZIFTI to the NCCN Guidelines in Oncology underscores the potential impact of KOMZIFTI for patients with R/R NPM1-mutated AML and supports our commitment to ensuring that patients have access to this important treatment option," said Mollie Leoni, M.D., Chief Medical Officer of Kura Oncology. "NPM1-mutated disease carries a substantial risk of relapse and historically poor outcomes in the relapsed or refractory setting. We are pleased to have received inclusion in the NCCN guidelines so rapidly after FDA approval and are committed to making KOMZIFTI available to patients in the United States." Kura Oncology is advancing zanzalintinib's development program in front-line AML treatment with the potential for combination with approved therapies to benefit a broader spectrum of patients earlier in their disease course. The company maintains a focus on pioneering advancements in menin inhibition and farnesyl transferase inhibition for high-need hematologic malignancies and solid tumors. SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) continues to advance its Phase 3 REGAL trial of GPS in acute myeloid leukemia patients who achieved complete remission following second-line salvage therapy, with final analysis anticipated by year-end 2025 once 80 deaths are reached. The company's Phase 2 data for SLS009, a selective CDK9 inhibitor, in combination with azacitidine and venetoclax for relapsed or refractory AML have been accepted for presentation at the American Society of Hematology (ASH) Annual Meeting in December 2025. "We remain highly encouraged by the continued, strong execution across our programs and the expanding body of clinical and preclinical data reinforcing the strength of our AML-focused pipeline," said Angelos Stergiou, MD, ScD h.c., President and CEO of SELLAS. "The Phase 3 REGAL trial of GPS is advancing as planned as highlighted by the key opinion leaders at our recent R&D event. Momentum around SLS009 also continues to build—our positive Phase 2 data were accepted for presentation at the upcoming ASH Annual Meeting, and we recently presented preclinical results at ESMO demonstrating clear survival benefits in T-PLL." SELLAS received approximately $54.6 million in gross proceeds from warrant exercises in September and October 2025, providing the company with $44.3 million in cash as of September 30, 2025, plus an additional $29.1 million received in October. The company plans to initiate an 80-patient trial in newly diagnosed first-line AML patients in the first quarter of 2026. TScan Therapeutics (NASDAQ: TCRX) reached agreement with the FDA on its pivotal trial design for TSC-101 following a productive end of Phase 1 meeting, with the agency approving a study design that mirrors the current ALLOHA Phase 1 trial using a biologically-assigned internal control arm expected to enable efficient enrollment and streamlined assessment of study endpoints. The company also implemented a commercial-ready manufacturing process that shortens manufacturing time by five days while lowering cost of goods and reducing ex vivo T cell expansion, with initial technology transfer to an external contract development and manufacturing organization completed. "Following a productive meeting with the FDA, we now have a clearly defined pivotal trial design for TSC-101, and we also have an improved commercial-ready manufacturing process in place," said Gavin MacBeath, Ph.D., CEO of TScan Therapeutics. "We are focused on advancing this promising program for patients with AML and MDS and look forward to sharing updated results from the ALLOHA Phase 1 trial at ASH next month." The company made the strategic decision to prioritize clinical development of its heme program and pause further enrollment in its PLEXI-T solid tumor Phase 1 trial while focusing preclinical efforts on in vivo engineering for solid tumors and target discovery in autoimmunity. With cash, cash equivalents, and marketable securities of $184.5 million as of September 30, 2025, TScan expects to fund operations into the second half of 2027, with plans to present updated clinical data including two-year relapse data at the upcoming 67th American Society of Hematology Annual Meeting and launch its pivotal trial for TSC-101 in the second quarter of 2026. Article Sources: CONTACT: USA NEWS GROUP [email protected] (604) 265-2873 DISCLAIMER: Nothing in this publication should be considered as personalized financial advice. We are not licensed under securities laws to address your particular financial situation. No communication by our employees to you should be deemed as personalized financial advice. Please consult a licensed financial advisor before making any investment decision. This is a paid advertisement and is neither an offer nor recommendation to buy or sell any security. We hold no investment licenses and are thus neither licensed nor qualified to provide investment advice. The content in this report or email is not provided to any individual with a view toward their individual circumstances. This article is being distributed by USA News Group on behalf of Market IQ Media Group Inc. ("MIQ"). MIQ has been paid a fee for GT Biopharma, Inc. advertising and digital media from Creative Digital Media Group ("CDMG"). There may be 3rd parties who may have shares of GT Biopharma, Inc., and may liquidate their shares which could have a negative effect on the price of the stock. This compensation constitutes a conflict of interest as to our ability to remain objective in our communication regarding the profiled company. Because of this conflict, individuals are strongly encouraged to not use this publication as the basis for any investment decision. The owner/operator of MIQ/BAY does not own any shares of GT Biopharma, Inc. but reserve the right to buy and sell, and will buy and sell shares of GT Biopharma, Inc. at any time without any further notice commencing immediately and ongoing. We also expect further compensation as an ongoing digital media effort to increase visibility for the company, no further notice will be given, but let this disclaimer serve as notice that all material, including this article, which is disseminated by MIQ has been approved on behalf of GT Biopharma, Inc. by CDMG; this is a paid advertisement, we currently own shares of GT Biopharma, Inc. and will buy and sell shares of the company in the open market, or through private placements, and/or other investment vehicles. While all information is believed to be reliable, it is not guaranteed by us to be accurate. Individuals should assume that all information contained in our newsletter is not trustworthy unless verified by their own independent research. Also, because events and circumstances frequently do not occur as expected, there will likely be differences between the any predictions and actual results. Always consult a licensed investment professional before making any investment decision. Be extremely careful, investing in securities carries a high degree of risk; you may likely lose some or all of the investment. SOURCES: 1. 2. 3. Logo - 21% more press release views with Request a Demo

点击蓝字 关注我们 邵凯迪1，张童越2，童军豪2，武爱文1（1 北京大学肿瘤医院暨北京市肿瘤防治研究所 胃肠肿瘤中心三病区 消化系统肿瘤整合防治全国重点实验室，北京 100142；2 北京大学医学部，基础医学院） 基金项目：国家自然科学基金项目（82173156）、北京市医管局登峰人才培养计划（DFL20241105）、北京市自然科学基金京津冀基础研究项目（22JCZXJC00140） 通信作者：武爱文　E-mail ：wuaw@sina.com 专家简介 武爱文  教授 北京大学肿瘤医院胃肠肿瘤中心三病区主任 主任医师，教授，博士研究生导师，博士后指导教师 中国抗癌协会第八届理事会理事 中华医学会外科学分会第十八届委员会实验外科学组委员 中国抗癌协会大肠癌专业委员会常务委员 中国抗癌协会胃癌专业委员会委员 中国抗癌协会肿瘤科普工作委员会副主任委员 北京抗癌协会大肠癌专业委员会主任委员 北京抗癌协会肿瘤科普专业委员会主任委员 世界中医药联合会整合肿瘤专业委员会副会长 中国医药教育协会腹部肿瘤专业委员会副主任委员 北京癌症防治学会直肠癌新辅助治疗专业委员会副主任委员 承担国家自然科学基金、国家重点研发计划项目子课题、京津冀基础研究合作专项、北京市科技新星项目、北京市医管中心215学科骨干、重点医学专业发展计划扬帆重点项目和登峰人才计划等。近五年牵头和参与临床研究58项，其中多中心项目31项 发表论文150篇，专利1项，主持或主要参与制定本领域专家共识21项 【摘要】结直肠癌是全球第三大常见癌症，构成重大健康挑战。2025年，其治疗领域以精准化、个体化为核心，呈现以下趋势：外科治疗趋向更精准、安全及个体化；围手术期治疗通过精确患者分层实现“降级与升级”；全程管理延伸至术后长期结构化运动与加速康复外科（ERAS）依从性保障；难治性肠癌治疗向基于分子检测的“多靶点、多模式、精准化”探索，分子分型是关键驱动力。人工智能（AI）在预后预测与治疗分层中展现潜力，助力精准临床决策。尽管取得显著进展，全面精准化、术后功能保护、患者分层及AI应用仍面临长期安全性、技术推广与复杂生物学机制等挑战。本文旨在回顾2025年度结直肠癌治疗进展并发掘现存问题。 【关键词】结直肠癌；精准化；结构化运动；器官保留；免疫治疗 结直肠癌是全球最常见的三大癌症之一，是癌症死亡的第二大原因，随着医学技术的不断进步和对疾病认识的持续深入，结直肠癌死亡率近年来持续下降，这也得益于结直肠癌治疗策略的趋势不断演变与优化[1,2]。随着医学技术的不断进步和对疾病认识的持续深入，结直肠癌治疗策略的趋势也在不断演变与优化。2025年是结直肠癌（CRC）治疗收获颇丰的一年，在手术技术、精准医疗、全程管理及转移性结直肠癌治疗探索等多个维度取得了突破性进展，为患者带来了显著的生存获益和生活质量改善。本文旨在汇总2025年度相关重要文献、学术会议报道，并征询部分专家的意见，围绕外科治疗精准化、结直肠癌全程管理、难治性肠癌的治疗探索、人工智能辅助治疗及现存的问题与挑战方面等进行总结，旨在为结直肠癌的多学科治疗提供最新进展信息。 一、2025年结直肠癌诊疗重要进展概述 1. 外科技术前沿 机器人手术在长期肿瘤学疗效上展现优势。REAL III期研究证实，机器人辅助腹腔镜手术（RALS）的3年局部区域复发率（1.6%）显著低于腹腔镜手术（4.0%），且系膜切除完整率更高，泌尿生殖功能保护更佳[3]。经肛门机器人内镜手术（ERSD）对深部病灶实现100%完整切除，术后恢复快[4]。 经肛全直肠系膜切除术（TaTME）地位巩固，作为低位直肠癌手术治疗的选择之一，TaLaR研究显示其3年无病生存期非劣于腹腔镜，且局部复发率更低（3.6%）[5]。 2. 围术期治疗前沿 治疗趋向精准个体化。循环肿瘤DNA（ctDNA）指导降级治疗：DYNAMIC研究5年随访确认，ctDNA阴性的II期患者豁免化疗后，5年无复发生存率达88%，与标准治疗组持平，证实了长期安全性[6]。 局部进展期直肠癌（LARC）方案优化：一项中国多中心II期研究发现，长程放化疗后“序贯”使用PD-1抑制剂，病理完全缓解率达32.7%，显著优于单纯放化疗组（14.0%），且毒性更可控[7]。 3. 全程管理前沿 结构化运动作为“第三种辅助治疗”地位确立。CHALLENGE研究显示，为期3年的结构化运动显著改善无病生存期（HR=0.72），并有延长总生存期趋势，应纳入标准康复指南[8]。 提升筛查参与率：TEMPO试验表明，在筛查邀请中设定简单“截止日期”（如2周内寄回），比复杂计划工具更能有效提升参与率[9]。 4．转移性结直肠癌治疗前沿 分子分型驱动治疗进展显著。BRAFV600E突变mCRC：BREAKWATER III期研究确立新一线标准，Encorafenib联合西妥昔单抗及mFOLFOX6化疗，将中位无进展生存期从7.1个月延长至12.8个月，中位总生存期翻倍（30.3个月 vs 15.1个月），客观缓解率达65.7%[10]。 MSI-H/dMMR mCRC：CheckMate 8HW研究证实，纳武利尤单抗联合伊匹木单抗一线治疗，相比单药显著提升客观缓解率（71% vs 58%）和完全缓解率（30%），降低38%疾病进展或死亡风险[11]。 MSS型mCRC：STELLAR-303 III期试验为“冷肿瘤”带来曙光，Zanzalintinib联合阿替利珠单抗在三线治疗中，相比瑞戈非尼显著延长总生存期（10.9个月 vs 9.4个月）[12]。 二、2025年结直肠癌诊疗重要趋势 1. 外科治疗的精准化与个体化趋势 内镜下治疗的精准风险分层 早期结直肠癌的内镜下黏膜下层剥离术（ESD）的安全性正通过精准风险分层模型得到保障。一项回顾性研究对ESD术前穿孔风险进行了量化，确定了三个独立的预测因子：病变纤维化（OR=2.67）、病变尺寸大于35毫米（OR=3.50），以及最主要的风险因素——术者早期经验（前100例手术，OR=14.6）。这项量化结果突出显示，ESD手术的安全性壁垒并非主要来自疾病本身的生理复杂性，而是操作者的技能和经验。极高的OR值（14.6）强烈提示ESD具有异常陡峭的学习曲线，因此，临床推广必须以标准化培训和分级授权制度为前提，才能有效保障ESD的安全性，并将其作为解决早期病变的技术手段[13]。 外科手术安全的精确性保障 外科治疗的焦点已从单纯的R0切除延伸至术中质量的量化控制和功能保护。一项前瞻性研究证实了术前3D虚拟血管建模（3DVM）与术中吲哚菁绿荧光造影（ICGPA）的互补价值。3DVM能够100%准确识别肠系膜血管变异，从而实现中央血管结扎（CVL）位置的精确规划。然而，研究强调3DVM提供的静态解剖模型不足以完全替代术中的功能验证。在25%的病例中，术中ICGPA提供了实时肠管灌注功能信息，促使术者调整了实际离断水平。表明CRC外科治疗当前核心趋势是追求动态功能验证，而非仅依赖静态解剖的精确性[14]。尽管IntAct RCT结果显示ICG的使用使吻合口漏（AL）发生率的相对风险降低29%（6.0% vs 8.5%），但统计学差异未达到显著性（P=0.07）[15]。尽管如此，这种下降趋势和对25%手术部位的实际干预，仍强调了实时血供评估对提高吻合口安全性的临床价值。此外，新型PGOT水凝胶的开发，通过物理密封、广谱抗菌和促进M2巨噬细胞转化三重机制，也展示了未来精准解决AL难题的潜力[16]。 2. LARC 的围手术期治疗趋向于精准的个体化 降级策略：FOWARC III期试验的10年随访更新为新辅助化疗的长期疗效提供了支持。该研究显示，新辅助mFOLFOX6单独化疗组与标准放化疗组在10年OS和局部复发率（LR）方面均无显著差异。这一发现提示，对于筛选出的中高位、局部复发风险不高的LARC患者，可以考虑省略放疗，实现治疗“降级”，以避免放疗对盆底功能和术后并发症带来的负面影响[17]。 升级策略（pMMR/MSS免疫增强）：鉴于大多数LARC患者属于错配修复完整（pMMR）的“冷肿瘤”，将免疫检查点抑制剂（ICIs）的疗效扩展至该群体成为热点。SPRING-01随机II期试验显示，短程放疗（SCRT）序贯CAPOX联合PD-1抑制剂信迪利单抗，将病理完全缓解（pCR）率提高至59.2%，远高于单纯CAPOX组的32.7%[18]。POLARSTAR试验的事后分析也显示，CRT联合PD-1阻断剂能够显著增强病理肿瘤退缩（TRG0 37% vs 18%），并显示出有利于器官保留的趋势[19]。特别值得注意的是，中国多中心II期临床试验明确了在nCRT结束后序贯给药的方案（pCR率32.7%）具有更可控的毒性，提示了在nCRT诱导肿瘤微环境转化后，ICI更能发挥其效应[7]。 侧方淋巴结（LLN）状态在TNT时代的预后意义：针对接受全程新辅助治疗（TNT）的远端直肠腺癌患者的研究发现，LLN阳性患者的5年DFS显著低于LLN阴性患者（58% vs 73%），但这种差异主要归因于远处转移率的显著升高（34% vs 20%），而不是局部控制失败。这一发现表明，在强化全身治疗的背景下，LLN阳性不再是单纯的局部控制指标，而更可能是全身性微转移疾病的强烈标志。因此，临床重点应转向强化全身辅助治疗，而非常规进行高发病率的LLN廓清术[20]。 器官保留策略的精准筛选与实施 器官保留策略（W&W，观察等待）的关键在于对患者进行精准分层。TORCH-E试验评估了iTNT方案（SCRT+CAPOX+特瑞普利单抗）针对低位T2-3bN0直肠癌的疗效，总完全缓解（CR）率高达72.7%，器官保留率（OP）达60.6%[21]。NICHE II期研究揭示了pMMR结肠癌在疾病早期对免疫治疗的可塑性，这对器官保留策略的筛选至关重要。研究发现，疗效预测与传统的肿瘤突变负荷（TMB）无关，反而与染色体基因组不稳定性、TP53突变且KRAS野生型和高基线增殖信号显著相关。此外，治疗耐药主要与“炎症-纤维化”TME亚型（富含TGF-β信号）相关。这一发现为低TMB的pMMR CRC免疫治疗提供了机制上的合理性，并提示未来的联合治疗应超越PD-1/CTLA-4轴，靶向克服基质障碍和TGF-β信号，以转化这些“冷”肿瘤[22]。 在影像学评估方面，针对系膜筋膜受累（MRF）的分子影像分型提升了MRI的预后指导意义。研究发现，并非所有MRF阳性患者面临相同的生存风险，其中MRF: TD+（肿瘤沉积累及）和MRF: EMVI+（壁外血管侵犯累及）是独立的不良预后因素。MRF: EMVI+亚型表现为较低的TMB和T细胞浸润少（“免疫冷”），而 MRF: TD+则与高Ki-67表达指数相关，反映了不同的生物学侵袭性[23]。 循环肿瘤DNA（ctDNA）指导辅助治疗的个体化 ctDNA作为分子残留病灶（MRD）的标志物，已成为辅助治疗个体化领域的核心仲裁者，正在形成一个覆盖I-IV期CRC的闭环精准决策系统。 ctDNA指导降级的长期安全性：DYNAMIC III期RCT的5年随访结果，以高级别证据确立了ctDNA在II期结肠癌中指导“分子降级”的可行性和安全性，通过ctDNA筛选出的MRD阴性II期患者，安全地避免辅助化疗后，其5年无复发生存期（RFS）为88%，与标准管理组的87%几乎一致。两组的5年总生存期（OS）也无显著差异（HR=1.05，P=0.887）[6]。 ctDNA指导升级的预后价值：GALAXY研究证实，术后ctDNA状态是比病理N分期更强的独立预后因子（HR高达9.96），ctDNA阳性患者从辅助化疗中获得了显著的生存获益（HR=0.28，P=0.031），而MRD阴性患者无显著获益。这为基于ctDNA的治疗“升级”（对MRD阳性患者强化治疗）提供相对合理的临床需求[24]。 ctDNA在mCRC中的动态预测价值：ctDNA的动态变化也具有预测免疫治疗疗效的潜力。SAMCO-PRODIGE 54 RCT的二次分析显示，治疗开始后1个月内的ctDNA早期变化对ICI治疗具有强大的预测能力，反应不良的患者疾病进展风险增加7倍以上[25]。CITRIC试验则证实ctDNA可作为指导RAS/BRAF野生型mCRC患者进行抗EGFR再挑战策略的生物标志物[26]。动态监测价值（如SAMCO）为临床试验设计提供了早期判断工具，能够针对无反应者及时转换方案，避免无效治疗[26]。 3. 结直肠癌全程管理趋势：运动干预与ERAS实践 运动干预的“第三种辅助治疗”地位：CHALLENGE III期RCT提供了结构化运动干预的I级证据，证实为期3年的结构化运动计划能显著延长结肠癌患者的DFS（HR=0.72），并伴有OS改善的趋势，确立了其继手术和化疗之后的“第三种辅助治疗”地位[8]。ASCOLT III期RCT未能证实每日200 mg阿司匹林能显著改善完成标准辅助化疗的高危II/III期CRC患者的5年DFS（HR=0.91，P=0.38）。这提示阿司匹林的二级预防作用可能需要更精细的分子分层（例如COX-2高表达）或更长的随访时间才能显现[27]。 ERAS依从性的剂量-效应关系：iCral前瞻性研究和Pisarska-Adamczyk回顾性研究均证实，ERAS的生存获益存在显著的“剂量-效应”关系。iCral研究发现，只有当ERAS依从率达到80.8%以上时，患者的长期OS才会显著改善，且该获益主要归因于非癌症相关死亡率的显著降低（高依从组 5.1% vs 低依从组 8.7%）。这一发现表明，围术期管理的质量控制（即高依从率）对长期生存的影响，主要通过提高患者的“健康储备”来实现，而非仅仅是癌症清除，强调了非肿瘤因素管理对长期预后的关键作用[28]。 4. 难治性肠癌（转移性结直肠癌）的治疗新趋势与探索 MSS/pMMR后线治疗的OS突破：TKI与ICI联合策略 对于占mCRC多数的MSS/pMMR患者，后线治疗一直难以获得OS获益。STELLAR-303 III期试验对比了新型多靶点TKI Zanzalintinib联合ICI阿替利珠单抗与标准三线疗法瑞戈非尼的疗效，结果显示联合方案在OS上取得了统计学显著性的改善，中位OS为10.9个月，优于瑞戈非尼组的9.4个月。这是首个在此类难治性人群中通过免疫联合方案证实有OS获益的III期试验，证明了TKI通过免疫调节作用“热化”冷肿瘤的策略是有效的[12]。 分子分型驱动的mCRC治疗革新 KRAS突变型mCRC与治疗时序：在2025年ASCO年会上，CodeBreaK 101试验评估了索托拉西布（KRAS G12C抑制剂）联合帕尼单抗和FOLFIRI化疗方案，在重度经治患者中取得了令人鼓舞的抗肿瘤活性，ORR达到57.5%，中位OS为17.9个月[29]。同时D3S-001 I期试验结果显示，这种新型KRAS抑制剂单药在初治CRC患者中取得了88.9%的ORR，提示其通过快速完全的靶点占有能够克服EGFR介导的KRAS再激活[30]。此外，一项II期单臂临床试验强调了抗血管生成药物时序的重要性，发现既往未接受贝伐珠单抗治疗（Bev-naïve）的KRAS突变患者，从PLK1抑制剂Onvansertib联合FOLFIRI和贝伐珠单抗的二线治疗中获益显著，提示既往贝伐珠单抗暴露可能导致对后续联合治疗的耐药[31]。 RAS/BRAF野生型mCRC：ANCHOR III期临床试验证实安罗替尼联合CAPOX疗效非劣于标准贝伐珠单抗联合CAPOX，两组中位PFS均为11.04个月，为患者提供了便捷的口服维持治疗替代方案[32]。 其他靶点：DeFianCe II期研究发现，靶向DKK1的单抗Sirexatamab联合标准治疗在DKK1高表达人群中显著改善了PFS和OS（HR=0.42），提示DKK1高表达可能成为该方案的富集生物标志物[33]。一项大规模汇总分析发现HER2扩增/过表达是独立的负面预后因子，但其状态并不具备对一线抗EGFR或贝伐珠单抗疗效的预测价值[34]。 结直肠癌腹膜转移（CRC-PM）的局部免疫探索 CRC-PM的围手术期管理趋势趋向规范化。腹腔灌洗细胞学（PLC）阳性结果与术后腹膜转移的发生率存在强关联，应被视为极高系统性复发风险因素[35]。CAIRO 6 III期RCT结果显示，对于可切除的单纯腹膜转移患者，围手术期系统治疗后行细胞减灭术（CRS）联合腹腔热灌注化疗（HIPEC），相比直接CRS联合HIPEC，未能显著改善OS，但显著延长了PFS（13.5个月 vs 7.0个月），支持对同步性病灶先行全身治疗的趋势[36,37]。此外，预防性洛铂腹腔热灌注化疗（IPIP）被证实可显著降低T4或N+高危患者的腹膜转移发生率[38]。单细胞技术揭示了CRC-PM微环境的局部免疫抑制机制。研究确定，腹膜免疫系统（PerIS）富集高度免疫抑制性的腹膜定居巨噬细胞（PRMs），它们通过分泌IL-10和VEGF等抑制性细胞因子，创建了有利于肿瘤生长的环境。这一发现提示，靶向耗竭PRMs有望与抗PD-1疗法产生协同作用[39]。此外，腹腔压力气雾化化疗（PIPAC）能诱导B/T淋巴细胞流入，并形成了三级淋巴结构（TLS），支持PIPAC-奥沙利铂与ICIs联合用于难治性腹膜转移[40]。 5. 结直肠癌与人工智能的结合趋势 AI辅助临床决策的真实世界转化 人工智能（AI）在CRC领域的应用已展示了在在真实世界中提高决策水平的潜力。Rosen等人利用丹麦国家登记数据开发的AI模型，成功预测术后1年死亡率，并将其嵌入临床实践以指导个性化围手术期优化护理。结果显示，接受AI辅助的患者严重并发症（CCI >20）发生率显著降低（从28.0%下降至19.1%），并实现了平均每位患者节省$2847的卫生经济学效益[41]。WINDOW研究中，Wang等人构建了名为“PATTERN-stageIII”的马尔可夫决策模型，评估了在荷兰医疗背景下，利用术后ctDNA状态结合临床病理特征（如pT、pN分期及血管侵犯情况）来豁免部分患者化疗的成本效益，进而实现治疗降级与个体化[42]。 AI通过识别高风险患者并提前干预，能够直接转化为可量化的临床和经济效益，为数据驱动的围手术期精准医疗提供了可扩展的实施范例。 影像组学AI在辅助治疗风险分层中的作用 AI在整合多维度数据以实现更高精度风险分层方面显示出优势。Huang等人提出的IRIS-CRC智能风险整合系统，结合了基于深度学习的影像组学特征与病理标志物。该系统能够将传统指南判定为“高危”的患者中27.1%“降级”为预后良好组（豁免不必要化疗），并识别传统“低危”人群中6.5%具有极高复发风险的隐匿性患者（治疗升级）。这种结合了影像学AI深度特征与病理指标的混合模型，提高了生存预测的准确性，成为II期CRC辅助治疗决策的有力工具[43]。 三、结直肠癌诊疗面临的挑战与未解难题 尽管CRC治疗已经取得了显著进展，但全面精准化、功能保护、患者精准分层和结合人工智能仍面临着来自长期安全性、技术推广、以及复杂生物学机制的诸多挑战。 1. 免疫治疗和等待观察的长期安全性与不良反应问题 辅助免疫治疗的毒性增加与远期OS数据的缺乏 ATOMIC研究虽然在DFS上取得显著成就，但同时揭示了辅助免疫治疗带来的不良反应问题。mFOLFOX6联合阿替利珠单抗组的≥3级治疗相关不良反应发生率为43.1%，高于单纯化疗组的35.9%。这种毒性增加要求临床医生必须提高对免疫相关不良事件（irAEs）的识别、诊断和长期管理能力，以确保患者能从长期DFS获益中得到最大的净临床益处。更关键的是，该研究的总生存（OS）数据尚未成熟，中位随访时间仅为42.5个月。这种后续治疗对OS结果的潜在影响是巨大的[44]。 器官保留策略的长期功能结局与二次挽救手术的影响 W&W策略已在LARC中显示出肿瘤学上的可行性和安全性。CAO/ARO/AIO-12和OPRA RCT的汇总分析显示，选择性W&W策略在DFS、DRFS和OS方面与强制性TME治疗表现出等效性[45]。此外，TAUTEM III期RCT也证实，对于早期LARC，CRT后行TEM在5年肿瘤控制上非劣于TME，且术后并发症发生率显著降低[46]。然而，W&W策略的核心挑战在于评估其长期功能性结局。尽管避免了TME，但新辅助治疗本身（特别是放疗）可能导致长期的排便功能障碍（如LARS），性功能和泌尿功能损伤。目前，对于成功实现器官保留和后续接受挽救性手术的患者，其长期的功能性结局缺乏标准化的评估体系，使临床决策无法全面权衡肿瘤学安全与生活质量。 2. 结直肠癌局部再生的转移问题 器官保留策略的最大风险在于局部再生（LR）。虽然CAO/ARO/AIO-16研究显示，LR患者可以成功接受挽救性R0切除，且其非再生无病生存率与直接TME患者无统计学差异[45]。但是Fernandez等人的研究对比了W&W后发生LR的患者与新辅助治疗后立即接受手术且病理反应良好（MPR，≤10%残留肿瘤）的患者。结果显示，LR组的DM显著高于立即手术组（22.8% vs 10.2%，P≤0.001），且3年DMFS显著更差（75% vs 87%）。 这一发现揭示了：局部再生本身可能不是单纯的局部控制失败，而是代表微小残留病灶在体内经历了一段等待时间，获得了更强的系统性侵袭潜能。这提示局部再生长本身可能是远处转移（Distant Metastases，DM）的独立风险因素，需要更深入地探索LR的分子机制[47]。 3. 早期的结直肠癌中，内镜下切除的界限 内镜下切除术，特别是ESD，在治疗低风险、局限性病变方面具有明确的优势。然而，其临床适应症的边界仍存在争议，核心在于识别直径大于20毫米的早期直肠肿瘤是否符合“内镜根治标准”。 DSETAMIS-2018 RCT首次直接对比了ESD与经肛门微创手术（TAMIS）的疗效，已支持ESD在局部复发率方面非劣于TAMIS，而且ESD在次要终点上展现出显著优势，包括更高的技术成功率（100% vs 88.9%）、更短的住院时间（中位数1天 vs 2天），以及显著更低的总体治疗成本。但ESD的学习曲线陡峭，对术者经验要求高，术者的早期经验是最大的穿孔风险因素[48]。 4. 机器人手术与TATME手术的使用适应症与证据的优化 机器人辅助腹腔镜手术（RALS）和TaTME因能克服深盆腔操作的技术限制，在中低位直肠癌手术中展现出优势，并在长期肿瘤学预后和功能保护上获得了高级别证据。尽管REAL研究提供了关键的III期随机对照数据，但其局限性也需注意：首先围手术期治疗方案不统一，不同中心放化疗方案的差异可能影响疾病预后。其次术者手术量不均衡，13名外科医生中，少数几位医生的手术量占比较高（1名医生约占30%，3名医生各约占10%），可能存在潜在偏差。最后研究人群单一：所有患者均为中国成年人，其特征（如BMI）可能与其他国家或种族的患者不同。RALS的推广仍面临挑战：RALS的优势主要体现在高难度、深盆腔手术中，在高位或标准结肠手术中的优势不明显。高昂的投资和维护成本，以及严格的术者培训要求，是其在全球范围普及的主要障碍[3]。 5. 细胞治疗的现有问题 CAR-T和TIL等细胞治疗在血液肿瘤中获巨大成功，但在结直肠癌（CRC）等实体瘤中仍面临挑战。核心障碍在于：高度免疫抑制的TME：CRC的肿瘤微环境（TME）分泌IL-10、TGF-β等抑制性因子，并招募MDSCs、TAMs等细胞，抑制T细胞功能。抗原异质性：靶向GUCY2C等肿瘤相关抗原（TAA）时，易发生肿瘤细胞亚群逃逸或“靶点丢失”。若TAA在正常组织低表达，还可能引发“脱靶毒性”。尽管存在挑战，具创新性的是，CRISPR-Cas9基因编辑TILs：靶向细胞内检查点CISH的基因编辑TILs，在一名双重抑制剂耐药的MSI-H患者中获得了超过21个月的持续完全缓解。但这仍是I期临床试验的初步结果。细胞治疗走向临床实践的障碍还包括大规模制备的高成本、工艺的标准化，以及普遍毒性（如CRS）的控制[49]。 6. 人工智能的局限性 尽管AI在CRC领域展示了预测风险和优化流程的强大能力，但其在临床推广和普适性方面仍存在根本性问题。普适性方面，成功的AI模型（如Rosen研究中预测术后死亡率的模型）依赖于高质量的数据源，例如丹麦的国家注册数据库。在大多数医疗系统中，电子病历系统不统一，数据互操作性差，导致AI模型在跨中心数据环境中的普适性受到严重限制。成本效益方面，PATTERN-stageIII马尔可夫决策模型揭示了ctDNA指导的降级策略（一种AI辅助的精准决策）在当前技术下缺乏成本效益。所以AI辅助策略该模型推广的两个主要障碍：一是检测本身的高昂成本；二是ctDNA阴性患者中仍存在不可忽视的复发风险（即检测灵敏度不足导致假阴性）[42]。所以，AI辅助策略的推广不仅要解决技术问题，还必须克服诊断工具的经济障碍。 四． 总结与展望 2025年结直肠癌治疗呈现出以分子分型和精准量化为核心的个体化管理趋势。在转移性疾病中，BRAFV600E突变患者OS的显著改善和MSI-H/dMMR患者双免疫疗法的确立，代表了分子分型驱动治疗的成熟。在早期疾病中，ctDNA指导的降级治疗和影像组学AI的风险分层，使辅助治疗决策更加精细。同时，结构化运动和ERAS高依从性等全程管理措施，被提升至影响长期生存的一级证据地位。然而，治疗的进步也带来了新的挑战。LARC器官保留的长期功能评估和局部再生所代表的系统性转移风险，仍是未解难题，需要更深入的生物学机制探索。未来的研究焦点应集中在深入解析pMMR/MSS“冷肿瘤”的免疫逃逸机制、精准识别内镜治疗的临床适应症、将局部再生（LR）视为系统性风险标志、突破细胞治疗走向临床实践的障碍、克服AI模型在跨中心数据环境中的普适性限制等方面，为结直肠癌患者更好的生活质量和预后提供更多的动力和可能。 【参考文献】 References [1]HAN B, ZHENG R, ZENG H, et al. Cancer incidence and mortality in China, 2022 [J]. Journal of the National Cancer Center, 2024, 4(1): 47-53. [2]SIEGEL R L, KRATZER T B, GIAQUINTO A N, et al. Cancer statistics, 2025 [J]. CA: a cancer journal for clinicians, 2025, 75(1): 10-45. [3]FENG Q, YUAN W, LI T, et al. Robotic vs Laparoscopic Surgery for Middle and Low Rectal Cancer: The REAL Randomized Clinical Trial [J]. Jama, 2025, 334(2): 136-48. [4]ALIPOURIANI A, OZGUR I, BHATT A, et al. Early Experience With Endorobotic Submucosal Dissection (ERSD): Pathologic and Short-term Outcomes in the First 28 Patients [J]. Annals of surgery, 2025, 281(5): 884-9. [5]ZENG Z, LUO S, ZHANG H, et al. Transanal vs Laparoscopic Total Mesorectal Excision and 3-Year Disease-Free Survival in Rectal Cancer: The TaLaR Randomized Clinical Trial [J]. Jama, 2025, 333(9): 774-83. [6]TIE J, WANG Y, LO S N, et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial [J]. Nature medicine, 2025, 31(5): 1509-18. [7]YANG Y, PANG K, LIN G, et al. Neoadjuvant chemoradiation with or without PD-1 blockade in locally advanced rectal cancer: a randomized phase 2 trial [J]. Nature medicine, 2025, 31(2): 449-56. [8]COURNEYA K S, VARDY J L, O'CALLAGHAN C J, et al. Structured Exercise after Adjuvant Chemotherapy for Colon Cancer [J]. The New England journal of medicine, 2025, 393(1): 13-25. [9]ROBB K A, YOUNG B, MURPHY M K, et al. Behavioural interventions to increase uptake of FIT colorectal screening in Scotland (TEMPO): a nationwide, eight-arm, factorial, randomised controlled trial [J]. Lancet (London, England), 2025, 405(10484): 1081-92. [10]ELEZ E, YOSHINO T, SHEN L, et al. Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer [J]. The New England journal of medicine, 2025, 392(24): 2425-37. [11]ANDRé T, ELEZ E, LENZ H J, et al. Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial [J]. Lancet (London, England), 2025, 405(10476): 383-95. [12]HECHT J R, PARK Y S, TABERNERO J, et al. Zanzalintinib plus atezolizumab versus regorafenib in refractory colorectal cancer (STELLAR-303): a randomised, open-label, phase 3 trial [J]. Lancet (London, England), 2025, 406(10517): 2360-70. [13]ULKUCU A, LAPORTE M, KHAN I, et al. Stratifying Endoscopic Submucosal Dissection Risks: A Validated Perforation Preoperative Risk Scoring Tool [J]. Annals of surgery, 2025. [14]KEARNS E C, MOYNIHAN A, KHAN M F, et al. Comparison and impact of preoperative 3D virtual vascular modelling with intraoperative indocyanine green perfusion angiography for personalized proximal colon cancer surgery [J]. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 2025, 51(3): 109581. [15]JAYNE D, CROFT J, CORRIGAN N, et al. Intraoperative fluorescence angiography with indocyanine green to prevent anastomotic leak in rectal cancer surgery (IntAct): an unblinded randomised controlled trial [J]. The lancet Gastroenterology & hepatology, 2025, 10(9): 806-17. [16]ZHU Y, BEI Z, LUO T, et al. Tissue-adhesive, antibacterial, and macrophage-reprogramming hydrogel for sealing colorectal anastomotic leakage and promoting healing [J]. Journal of materials chemistry B, 2025, 13(30): 9081-99. [17]ZHANG J, CHI P, SHI L, et al. Neoadjuvant Modified Infusional Fluorouracil, Leucovorin, and Oxaliplatin With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Updated Results of the FOWARC Study After a Median Follow-Up of 10 Years [J]. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2025, 43(6): 633-40. [18]TIAN F, DAI H, SHA D, et al. Total neoadjuvant treatment with short-course radiotherapy followed by sintilimab plus capecitabine-oxaliplatin versus short-course radiotherapy followed by capecitabine-oxaliplatin in patients with locally advanced rectal cancer (SPRING-01): a single-centre, open-label, phase 2, randomised controlled trial [J]. The Lancet Oncology, 2025, 26(8): 1043-54. [19]PANG K, LIU X, YAO H, et al. Impact of PD1 blockade added to neoadjuvant chemoradiotherapy on rectal cancer surgery: post-hoc analysis of the randomized POLARSTAR trial [J]. The British journal of surgery, 2025, 112(3). [20]BEETS N R A, VERHEIJ F S, WILLIAMS H, et al. Association of Lateral Pelvic Lymph Nodes with Disease Recurrence and Organ Preservation in Patients with Distal Rectal Adenocarcinoma Treated with Total Neoadjuvant Therapy [J]. Annals of surgery, 2025, 282(2): 311-8. [21]XIA F, CHEN Y, ZHOU D, et al. Organ preservation via immunotherapy-based total neoadjuvant therapy in early low rectal cancer (TORCH-E): a multicenter, open-label, single-arm, phase 2 study [J]. Clin Cancer Res, 2025. [22]TAN P B, VERSCHOOR Y L, VAN DEN BERG J G, et al. Neoadjuvant immunotherapy in mismatch-repair-proficient colon cancers [J]. Nature, 2025. [23]FENG Y, HU T, GU W, et al. Mesorectal Fascia Involvement by Tumor Deposits or Extramural Vascular Invasion at MRI Predicts Prognosis in Rectal Cancer [J]. Radiology, 2025, 317(1): e243627. [24]ANDO K, HAMABE A, NAKAMURA Y, et al. Molecular Residual Disease and Recurrence in Rectal Cancer Patients Undergoing Upfront Surgery: A Prospective Cohort Study [J]. Annals of surgery, 2025. [25]TAïEB J, SULLO F G, LECANU A, et al. Early ctDNA and Survival in Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors: A Secondary Analysis of the SAMCO-PRODIGE 54 Randomized Clinical Trial [J]. JAMA oncology, 2025, 11(8): 874-82. [26]MONTAGUT C, VIDAL J, RODRIGUEZ C F, et al. LBA33 Circulating tumor (ct) DNA-guided anti-EGFR rechallenge strategy in metastatic colorectal cancer (mCRC): Final results of the phase II randomized CITRIC trial [J]. Annals of Oncology, 2025, 36: S1691-S2. [27]CHIA J W K, SEGELOV E, DENG Y, et al. Aspirin after completion of standard adjuvant therapy for colorectal cancer (ASCOLT): an international, multicentre, phase 3, randomised, double-blind, placebo-controlled trial [J]. The lancet Gastroenterology & hepatology, 2025, 10(3): 198-209. [28]PISARSKA-ADAMCZYK M, ZAWADZKA K, TORBICZ G, et al. Does high compliance with the enhanced recovery after surgery protocol improve 5-year survival? A cohort study of 468 nonmetastatic colorectal cancer patients [J]. Polish archives of internal medicine, 2025, 135(5). [29]STRICKLER J H, KUBOKI Y, HONG D S, et al. Long-term safety and efficacy of sotorasib plus panitumumab and FOLFIRI for previously treated KRAS G12C-mutated metastatic colorectal cancer (mCRC): CodeBreaK 101 (phase 1b) [J]. Journal of Clinical Oncology, 2025, 43(16_suppl): 3506-. [30]CHO B C, LU S, LEE M A, et al. D3S-001 in advanced solid tumors with KRAS(G12C) mutations: a phase 1 trial [J]. Nature medicine, 2025, 31(8): 2768-77. [31]AHN D H, RIDINGER M, CANNON T L, et al. Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial [J]. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2025, 43(7): 840-51. [32]DING K-F, LIU Y, ZHANG Y, et al. Anlotinib versus bevacizumab added to standard first-line chemotherapy among patients with RAS/BRAF wild-type, unresectable metastatic colorectal cancer: A multicenter, prospective, randomised, phase 3 clinical trial (ANCHOR trial) [J]. Journal of Clinical Oncology, 2025, 43(17_suppl): LBA3502-LBA. [33]WAINBERG Z A A, HAN S W, KIM J G, et al. LBA34 DeFianCe trial: A randomized phase II trial of sirexatamab (DKN-01) plus bevacizumab and chemotherapy versus bevacizumab and chemotherapy as second-line therapy in advanced microsatellite stable (MSS) colorectal cancer (CRC) [J]. Annals of Oncology, 2025, 36: S1692-S3. [34]GERMANI M M, BORELLI B, HASHIMOTO T, et al. Impact of Human Epidermal Growth Factor Receptor 2 in Patients With Metastatic Colorectal Cancer Treated With Chemotherapy Plus Bevacizumab or Anti-EGFRs: Exploratory Analysis of Eight Randomized Trials [J]. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2025, 43(29): 3184-97. [35]KONG D, LI Y, YIN S, et al. Peritoneal Lavage Cytology Predicts Peritoneal Metastasis and is Associated with Poor Prognosis in Patients with Stage II-III Colorectal Cancer [J]. Annals of surgical oncology, 2025, 32(13): 9712-22. [36]ROVERS K, BAKKERS C, VAN DEN HEUVEL T B M, et al. Perioperative systemic therapy for resectable colorectal peritoneal metastases: A multicenter randomized phase 3 trial (CAIRO6) [J]. Journal of Clinical Oncology, 2025, 43(16_suppl): 3505-. [37]SCHULTZ K S, BANSAL V V, WACH M M, et al. Consensus Guideline for the Management of Colorectal Cancer with Peritoneal Metastases [J]. Annals of surgical oncology, 2025. [38]BRIèRE R, SIMARD A J, ROULEAU-FOURNIER F, et al. Perioperative management and survival outcomes following cytoreductive surgery in patients with peritoneal metastases from rectal cancer: A scoping review [J]. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 2025, 51(2): 109498. [39]SARIS J, LI YIM A Y F, BOOTSMA S, et al. Peritoneal resident macrophages constitute an immunosuppressive environment in peritoneal metastasized colorectal cancer [J]. Nature communications, 2025, 16(1): 3669. [40]CONSTANTINIDES A, LANSU N, MOSEN P, et al. Treatment of colorectal peritoneal metastases with oxaliplatin induces biomarkers predicting response to immune checkpoint blockade [J]. Translational oncology, 2025, 59: 102464. [41]ROSEN A W, OSE I, GöGENUR M, et al. Clinical implementation of an AI-based prediction model for decision support for patients undergoing colorectal cancer surgery [J]. Nature medicine, 2025, 31(11): 3737-48. [42]WANG H, KRAMER A, GREUTER M J E, et al. CtDNA-guided de-escalation of adjuvant chemotherapy in stage III colon cancer: early model-based evaluation of cost-effectiveness [J]. Therapeutic advances in medical oncology, 2025, 17: 17588359251384238. [43]HUANG Y Q, CHEN X B, CUI Y F, et al. Enhanced risk stratification for stage II colorectal cancer using deep learning-based CT classifier and pathological markers to optimize adjuvant therapy decision [J]. Annals of oncology : official journal of the European Society for Medical Oncology, 2025, 36(10): 1178-89. [44]SINICROPE F A, OU F-S, ARNOLD D, et al. Randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III deficient DNA mismatch repair (dMMR) colon cancer (Alliance A021502; ATOMIC) [J]. Journal of Clinical Oncology, 2025, 43(17_suppl): LBA1-LBA. [45]WILLIAMS H, FOKAS E, DIEFENHARDT M, et al. Survival among patients treated with total mesorectal excision or selective watch-and-wait after total neoadjuvant therapy: a pooled analysis of the CAO/ARO/AIO-12 and OPRA randomized phase II trials [J]. Annals of oncology : official journal of the European Society for Medical Oncology, 2025, 36(5): 543-7. [46]SERRA-ARACIL X, PERICAY C, CIDONCHA A, et al. Chemoradiotherapy and Local Excision vs Total Mesorectal Excision in T2-T3ab, N0, M0 Rectal Cancer: The TAUTEM Randomized Clinical Trial [J]. JAMA surgery, 2025, 160(7): 783-93. [47]FERNANDEZ L M, SãO JULIãO G P, SANTACRUZ C C, et al. Risks of Organ Preservation in Rectal Cancer: Data From Two International Registries on Rectal Cancer [J]. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2025, 43(14): 1663-72. [48]DE FRUTOS ROSA D, ALONSO SEBASTIáN I, BARQUERO DECLARA D, et al. A Randomized Trial of Endoscopic Submucosal Dissection vs Transanal Minimally Invasive Surgery in Early Rectal Neoplasms: DSETAMIS-2018 Study [J]. Gastroenterology, 2025. [49]LOU E, CHOUDHRY M S, STARR T K, et al. Targeting the intracellular immune checkpoint CISH with CRISPR-Cas9-edited T cells in patients with metastatic colorectal cancer: a first-in-human, single-centre, phase 1 trial [J]. The Lancet Oncology, 2025, 26(5): 559-70. 推荐阅读 ●   盘点2024丨武爱文教授：2024年度结直肠癌治疗研究进展 ●   盘点2023 | 武爱文教授：2023年度结直肠癌治疗研究进展 ●   盘点2022丨武爱文教授：2022年度结直肠癌治疗进展 ●   2024年度肿瘤学科盘点集锦(共17个) 声明：本文由“肿瘤界”整理与汇编，欢迎分享转载，如需使用本文内容，请务必注明出处。 编辑：lagertha 审核：武爱文教授