预约演示

更新于：2025-08-25

Temozolomide

替莫唑胺

更新于：2025-08-25

概要

基本信息

药物类型

小分子化药

别名

3,4-dihydro-3-methyl-4-oxoimidazo(5,1-d)-1,2,3,5-tetrazine-8-carboxamide、3,4-dihydro-3-methyl-4-oxoimidazo(5,1-d)-as-tetrazine-8-carboxamide、3-methyl-4-oxo-3,4-dihydroimidazo(5,1-d)(1,2,3,5)tetrazine-8-carboxamide

+ [27]

靶点

DNA

作用方式

抑制剂

作用机制

DNA抑制剂(DNA抑制剂)、DNA烷化剂

治疗领域

肿瘤神经系统疾病皮肤和肌肉骨骼疾病+ [10]

在研适应症

尤文肉瘤脑恶性胶质瘤转移性恶性黑色素瘤+ [84]

非在研适应症

听神经瘤伴有 11q23 异常的急性髓系白血病肾上腺嗜铬细胞瘤+ [97]

原研机构

Merck Sharp & Dohme Corp.

在研机构

National Cancer InstituteSun Pharmaceutical Industries (Europe) BV

Genentech, Inc.

+ [28]

非在研机构

Hexal AG

Duke University

The Fox Chase Cancer Center

+ [39]

权益机构

Double Bond Pharmaceutical International AB

Institut Gustave Roussy EURL

Belarusian State University

+ [1]

最高研发阶段批准上市

首次获批日期

欧盟 (1999-01-26),

星形细胞瘤多形性胶质母细胞瘤胶质瘤

最高研发阶段(中国)批准上市

特殊审评孤儿药 (美国)、孤儿药 (欧盟)、优先审评 (中国)、加速批准 (美国)

登录后查看时间轴

结构/序列

分子式C6H6N6O2

InChIKeyBPEGJWRSRHCHSN-UHFFFAOYSA-N

CAS号85622-93-1

关联

1,061

项与替莫唑胺相关的临床试验

NCT01777919

/ Not yet recruiting临床2期IIT

A PHASE II CLINICAL TRIAL FOR THE EVALUATION OF THE EFFICACY OF DISULFIRAM/COPPER COMBINATION AS AN ADJUVANT AND CONCURRENT CHEMOTHERAPY IN THE TREATMENT OF NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORM

Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Despite maximal treatment tumor relapse occurs regularly accompanied by unfavourable prognosis. Among other reasons, it is believed that this could be in part due to the existence of the so-called tumor stem cells (TSCs), a cellular subfraction within GBM which escape therapy by being highly resistant to irradiation and chemotherapy and thus constituting the source of tumor recurrence.
GBM, like many other cancers, show a sub-population of aldehyde dehydrogenase (ALDH) overexpressing TSCs. More specifically, ALDH1A1, a cytoplasmatic isoform of ALDH, proved to be a novel stem cell marker in human GBM. In addition, ALDH1A1 has been shown to be a mediator for resistance of GBM to temozolomide (TMZ) and a reliable predictor of clinical outcome; prognosis of patients with a high level of ALDH1A1 expression was poor compared with that of patients with low levels. Consequently, ALDH1A1 may serve as a potential target to improve treatment of human GBM through inhibition of the enzyme.
Disulfiram (DSF) has been used for more than sixty years in the treatment of chronic alcoholism because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver ALDHs. Actually, DSF is a strong inhibitor of ALDH1A1 and relatively non-toxic at therapeutic (for chronic alcoholism) doses that can penetrate the blood-brain barrier. In addition, DSF has been shown to be cytotoxic on GBM stem-like cells, inhibiting the growth of TMZ resistant GBM cells and blocking self-renewal by
100% , while it has been identified as an inhibitor of human GBM stem cells in high-throughput chemical screens. Interestingly, a number of these actions were copper-dependent.
In the current Phase II clinical trial, DSF/copper combination will be tested as an adjunctive and concurrent chemotherapy in the treatment of newly diagnosed GBM. According to our hypothesis, initiation of DSF chemotherapy after the resection of the tumor and before the introduction of the standard radio-chemotherapy will inhibit ALDH1A1 of GBM TSCs making them more susceptible to radio-chemotherapy and possibly reducing the recurrence rate of GBM. On the other hand, the addition of copper will probably enhance the cytotoxic effects of DSF possibly through augmentation of its pro-apoptotic and proteasomal inhibitory actions.

开始日期2027-01-01

申办/合作机构

Universität Ulm

[+2]

NCT07120984

/ Not yet recruiting临床2期

A Phase II Study to Evaluate the Safety and Efficacy of L19TNF With Alkylating Chemotherapy for Patients With Recurrent IDH-mutant Astrocytoma or Oligodendroglioma

The purpose of this study is to explore the safety and efficacy of the antibody-cytokine fusion protein L19TNF alone or in combination with alkylating chemotherapy in patients with recurrent IDH mutant glioma.

开始日期2026-01-30

申办/合作机构

Philogen SpA

NCT07085338

/ Not yet recruiting临床2期IIT

A Phase II Study With a Safety Run-In of the Addition of N-803, a Novel IL-15 Super-Agonist, to a Chemoimmunotherapy Backbone for the Treatment of Patients With Relapsed or Refractory Neuroblastoma

The study participant is being asked to take part in this research study because the participant has been diagnosed with neuroblastoma that did not fully respond to previous treatment (refractory), or it has returned after treatment (relapsed).
Primary Aims
* To evaluate if the administration of N-803 in combination with irinotecan, temozolomide, hu14-18K322A, and GM-CSF in patients with relapsed/refractory neuroblastoma is feasible and tolerable
* To determine if the response rate of N-803 with irinotecan, temozolomide, hu14.18K322A and GM-CSF in patients with relapsed/refractory neuroblastoma is superior to the combination of irinotecan, temozolomide, hu14.18K322A, and GM-CSF
Secondary Aims
* To describe the toxicity profile of N-803 administered with irinotecan, temozolomide, hu14.18K322A and GM-CSF
* To evaluate and compare the progression free survival (PFS) and overall survival (OS) of and between patients receiving irinotecan, temozolomide, hu14.18K322A and GM-CSF with and without N-803

开始日期2025-12-01

申办/合作机构

St. Jude Children's Research Hospital, Inc.

100 项与替莫唑胺相关的临床结果

登录后查看更多信息

100 项与替莫唑胺相关的转化医学

登录后查看更多信息

100 项与替莫唑胺相关的专利（医药）

登录后查看更多信息

13,791

项与替莫唑胺相关的文献（医药）

2026-01-01·TALANTA

A cell-permeable fluorescent probe for imaging of DNA repair protein ALKBH2

Article

作者: Anindya, Roy ; Rathnam, Sharan Shanmuga Vuppaladadium ; Khan, Faiz Ahmed ; Ray, Sandipan ; Rankawat, Sourbh ; Shaji, Unnikrishnan P ; Jangra, Jitender ; Khatua, Rashmi Ranjan

ALKBH2 is a key DNA repair enzyme that removes various methyl-adducts, including N1-methyl-adenine and N3-methyl-cytosine, from genomic DNA. ALKBH2 overexpression is observed in many cancer and leads to temozolomide resistance in glioblastoma cell lines. The growing significance of ALKBH2 as a promising therapeutic target in cancer has highlighted the need for suitable chemical tools to enable its detailed study and functional characterization. To address this gap, we developed a fluorescent probe for rapid and selective detection of ALKBH2 in live cancer cells. Building on our previously reported finding that the HIV protease inhibitor ritonavir selectively binds and inhibits ALKBH2, we synthesized a BODIPY-labeled ritonavir (rit-BD) as an imaging agent. Rit-BD showed peak absorption (A_max) and emission (E_max) to be 576 nm and 586 nm, respectively. Our results from the binding experiment demonstrate that rit-BD binds to ALKBH2 in vitro with micromolar affinity. The limit of detection (LOD) for ALKBH2 with Rit-BD was estimated to be 115 ng/ml (4.7 nM) with a linear range of 0.5-330 μg/ml (14 nM-10 μM). Furthermore, In vitro and in cellulo experiments and live-cell imaging confirmed that rit-BD could be used to label ALKBH2 in the living cell nucleus. Our findings establish rit-BD as a unique dual-purpose agent for visualizing ALKBH2 dynamics and inhibiting DNA repair activity in cancer cells.

2025-12-31·Human Vaccines & Immunotherapeutics

Trends in the immunotherapy for glioblastoma: A two-decade bibliometric analysis

Article

作者: Wang, Hongxin ; Yan, Wei ; Long, Zhi ; Yi, Zhenjie

Glioblastoma is a life-threatening primary malignant brain tumor with an unfavorable prognosis. Contributing factors to its poor outcome include tumor heterogeneity, low mutational burden, and immunosuppression within the tumor microenvironment. Recognizing these challenges, immunotherapeutic strategies have emerged as a promising avenue for glioblastoma treatment. Although several dynamic research and scientific trend have increasingly taken pace in the immunotherapeutic approaches to glioblastoma, systematic bibliometric studies on such trends are few. On this note, this study explores a bibliometric analysis of the research hotspots and trends in glioblastoma immunotherapy. We conducted a search in the Web of Science Core Collection database for articles on glioblastoma immunotherapy published between 2004 and 2024. Using VOSviewer and CiteSpace software, we analyzed collected articles to explore aspects such as country of origin, journal of publication, affiliated institute, authorship, keywords, and citation patterns. As of May 1, 2024, we retrieved 3,729 papers on Glioblastoma Immunotherapy. In the field of glioblastoma immunotherapy, the United States stands out as the leading contributor, with 1,708 publications and a substantial 90,590 citations. Following closely, China has made significant contributions through 926 publications, earning 17,533 citations, while Germany adds to the body of knowledge with 349 publications and 16,355 citations. Furthermore, Authoritative journals in this field include Clinical Cancer Research and Neuro-Oncology. The top five keywords during this period were temozolomide, radiotherapy, dendritic cell, cytotoxic T lymphocyte, and vaccination. Moreover, Hotspots in the field include immune checkpoint inhibitors and chimeric antigen receptor T cell therapy.

2025-12-31·NMC case report journal

Favorable Response to Conventional Chemoradiotherapy in Radiation-induced Glioma Harboring Coamplification of PDGFRA, KIT, and KDR: A Case Report and Literature Review

Article

作者: MIZUNO, Reina ; KANEKO-MISHIMA, Masayo ; TANIKAWA, Daisuke ; SAKAKIBARA, Ayaka ; HOMMA, Taku ; SUZUKI, Tomonari ; MISHIMA, Kazuhiko ; OZAWA, Tatsuya ; SAKURADA, Kokyo ; KATO, Shingo ; FUKUOKA, Masayoshi ; EHARA, Takuro ; SHIRAHATA, Mitsuaki

One of the most serious complications of cranial radiotherapy is the development of radiation-induced glioma, which is estimated to occur in 1%-4% of patients who have received cranial irradiation and has a worse prognosis than sporadic glioblastoma. Although comprehensive genetic analysis has recently uncovered the molecular characteristics of radiation-induced glioma, the full picture remains unclear due to its rarity. A 45-year-old man presented with generalized seizures caused by multiple brain tumors involving the right frontal lobe, thalamus, and brainstem. The patient had a history of whole-brain radiotherapy for recurrent Burkitt's lymphoma at the age of 12. He underwent craniotomy, and the histological diagnosis revealed a high-grade glioma with isocitrate dehydrogenase-wildtype, which was presumed to be a radiation-induced glioma that developed 33 years after whole-brain irradiation. Next-generation sequencing identified a CDKN2A/B deletion, as well as coamplification of several receptor tyrosine kinases-encoding genes, including PDGFRA, KIT, and KDR, all of which are located at 4q12. Amplification of this region is broadly observed across cancers and is associated with poor prognosis in sporadic glioblastoma. Nevertheless, the patient received chemoradiotherapy with temozolomide, followed by temozolomide maintenance therapy, resulting in a complete response of all lesions. Although radiation-induced gliomas are generally difficult to treat, our patient unexpectedly responded well to conventional chemoradiotherapy despite the coamplification of multiple receptor tyrosine kinases-encoding genes, which is typically suggestive of an aggressive phenotype. Our case indicates that some radiation-induced gliomas may have distinct molecular characteristics influencing the therapeutic response, which differ from those of sporadic glioblastomas.

690

项与替莫唑胺相关的新闻（医药）

2025-08-21

·Biotech前瞻

“癌王”胰腺癌突破在即丨电场治疗递交 FDA 上市前批准申请

点击蓝字关注我们本期看点胰腺导管腺癌（PDAC）因其早期无明显症状、对传统放化疗耐受性高，治疗手段有限，整体患者生存期短，被誉为“癌中之王”。2025 ASCO上，Novocure公司的创新疗法肿瘤电场治疗（Tumor Treating Fields, TTFields）为“癌王”困境带来破局曙光，PANOVA‑3（NCT03377491）Ⅲ期临床试验，成为迄今为止首个在局晚期胰腺癌中成功取得OS获益的III期研究。标志着电场疗法在这一难治肿瘤领域的历史性突破。近日，Novocure 提交 FDA PMA 申请，用于局部晚期胰腺癌的 TTFields 治疗。除了胰腺癌，在其他肿瘤领域， TTFields是否有突破的可能性。本期内容 01 TTFields丨FDA快讯 02 2025 ASCO丨PANOVA-3研究 03 TTFields丨其他实体瘤研究进展 04 总结与展望【01 TTFields丨FDA快讯】 Novocure 提交 FDA PMA 申请，用于局部晚期胰腺癌的 TTFields 治疗提交申请： Novocure 已于 2025 年 8 月 20 日向 FDA 提交 Premarket Approval（PMA）申请，以推进其 Tumor Treating Fields（TTFields）疗法用于局部晚期不可切除胰腺癌的治疗 (BioSpace)。提交依据：该申请基于 III 期 PANOVA‑3 临床试验数据，表明 TTFields 联合 gemcitabine + nab‑paclitaxel（GnP）显著延长了患者的整体生存期（OS：16.2 个月 vs 14.2 个月，HR 0.82，P = 0.039）(OncLive)。安全性：治疗耐受性良好，无新增安全信号，最常见的是轻至中度皮肤不良反应。审批展望：Novocure 预计 FDA 将在 2026 年下半年对该申请做出审批决定。在2025ASCO大会上，PANOVA-3研究详细数据进行了展示。【02 2025 ASCO丨PANOVA-3研究】标题： PANOVA-3 研究：一项关于肿瘤电场治疗（TTFields）联合吉西他滨和白蛋白紫杉醇用于局部晚期胰腺导管腺癌（LA-PAC）的三期临床试验。背景： LA-PAC，临床治疗高度未满足胰腺导管腺癌5年OS率仅8%, 临床需求仍未被满足。约30-35%的患者诊断时即为局部进展期，其中仅10-15%的患者可行根治性手术切除。余下患者无法进行根治手术切除，会出现严重的疾病症状，尤其是癌痛。目前局部晚期胰腺癌患者标准治疗是化疗(GnP, FOLFIRINOX, NALIRIFOX) ±放疗。目前大多数探索新型药物的临床研究都聚焦在转移性胰腺癌领域, 在LA-PAC中开展的临床研究未获得突破, 对比标准治疗未观察到OS获益。迄今为止，尚无三期临床试验能在局部晚期胰腺腺癌（LA-PAC）患者中证实其总生存期（OS）有获益。模拟示意图 TTFields疗法 TTFields是一种肿瘤电场疗法，能够干扰癌细胞分裂, 诱导增强肿瘤免疫反应。TTFields疗法指通过皮肤传感器阵列, 将交变电场无创传递至肿瘤部位。TTFields联合系统治疗已经在欧洲和美国获批用于胶质母细胞瘤，恶性胸膜间皮瘤和转移性非小细胞肺癌, 在日本也获批用于胶质母细胞瘤治疗。 II期PANOVA预试验结果提示, TTFields联合吉西他滨±白蛋白紫杉醇治疗晚期胰腺导管腺癌临床有效且可耐受。在此，研究团队报告了迄今为止规模最大的全球性三期、随机、开放标签的LA-PAC临床试验PANOVA-3（NCT03377491）的最终数据。方法：研究设计新诊断为不可切除的局部晚期胰腺导管腺癌（LA -PAC）的成年患者，以 1:1 的比例随机分为两组，一组接受肿瘤电场治疗（150 kHz，18h/d）联合吉西他滨/白蛋白紫杉醇（GnP）治疗，另一组仅接受GnP治疗。主要终点是OS。次要终点包括PFS、局部无进展生存期（local PFS）、ORR和无痛生存期。试验后期评估了远处无进展生存期（distant PFS）（胰腺外及区域淋巴结外的转移）。结果：患者分配患者基线共571名患者参与随机分组。各研究组患者的基线特征总体较为均衡。主要终点：OS 与仅接受GnP治疗相比，接受TTFields联合GnP治疗的患者OS显著延长（mOS分别为16.2个月和14.2个月；HR 0.82 ，p=0.039），达到了主要研究终点。TTFields联合GnP治疗组的一年生存率也显著高于仅接受GnP治疗组（分别为68.1% [95% CI：62.0 - 73.5] 和60.2% [95% CI：54.2 - 65.7]，p=0.029）。TTFields联合治疗可显著延长中位无疼痛生存期至15.2个月，较单纯化疗组的9.1个月整整延长了6.1个月（HR 0.74，P = 0.027），这一成果提示TTFields能够有效控制疼痛症状，极大地提升患者的生活质量。次要终点：PFS和句部PFS 两组间无进展生存期或局部无进展生存期无显著差异。总体安全性设备相关AEs 两组AEs发生率相当。在接受TTFields的患者中，81%出现了以皮肤毒性为主的设备相关不良事件，但多数为1级或2级。结论：研究结果总结： PANOVA-3研究是首个治疗不可切除LA-PAC，取得OS获益的III期研究； TTFields生存获益与更好的生活质量评分以及更优的无疼痛生存结果有关； TTFields唯一常见AE是局部皮肤反应； TTFields联合GnP治疗具有成为不可切除LA-PAC新型治疗模式的潜力。研究局限性：疗效反应由研究者基于肿瘤影像进行评估；尽管方案中包含了基线时可切除性胰腺癌的明确定义，但未对随访访视提供此类指导；两组性别分布不均衡；两组在随机后第一个月内治疗中止率较高；对照组中位OS相比其他Ⅱ期和III期研究偏低；开放性设计胰腺癌适应症进度基于PANOVA-3研究数据，Novocure计划于2025年下半年在美国递交TTFields用于治疗不可切除局部晚期胰腺癌的上市许可申请，并同步计划在欧盟、日本及其他重点市场递交上市许可申请。再鼎医药参与了此项研究，并计划于2025年在中国提交上市许可申请。 03 TTFields丨其他实体瘤研究进展 TTFields领域进展最快的是Novocure公司，目前商业化了两款基于肿瘤电场技术的可穿戴设备：来源：Novocure公司官网 Optune® （原名 NovoTTF‑100A System）：适应症：用于治疗成人胶质母细胞瘤（GBM）。复发性 GBM（2011 年 FDA 批准）新诊断 GBM：与替莫唑胺（Temozolomide）联合，用于行最大切除术并完成放疗后的患者（2015年 FDA 批准）。新诊断GBM：TTFields+替莫唑胺将5年生存率从5%提升至30%（高依从性患者） TIGER研究（2024 ASCO）：中位OS 19.6个月，2年OS率42.4% Optune Lua® （原名 NovoTTF‑100L System）：恶性胸膜间皮瘤：一线联合培美曲塞 + 铂类化疗，用于不可切除的局部晚期或转移性恶性胸膜间皮瘤（MPM），是 15 年来首个获批此适应症的创新疗法（2019年5月23日，FDA 批准）。非小细胞肺癌：与 PD‑1/PD‑L1 抑制剂或多西他赛（Docetaxel）联合，用于在含铂化疗后出现进展的成人转移性非小细胞肺癌（mNSCLC）患者（2024年10月，FDA 批准）。肺癌适应症的批准源于III期LUNAR研究，该研究评估了Optune Lua联合PD-1/PD-L1抑制剂或多西他赛（试验组）与PD-1/PD-L1抑制剂或多西他赛单独（对照组）治疗在铂基治疗期间或之后进展的转移性非小细胞肺癌患者中的疗效。最终研究结果显示：电场联合治疗mOS为13.2 个月，PD-1/PD-L1抑制剂或多西他赛治疗组的mOS为9.9个月。 TTFields在卵巢癌中也有探索来源：Gynecologic Oncology 期刊一项共纳入31例复发性卵巢癌患者的II期INNOVATE研究发表于Gynecologic Oncology 期刊，研究结果显示：TTFields+紫杉醇治疗铂耐药复发卵巢癌的中位PFS达8.9个月（历史对照仅3-4个月）。效果显著。但由于是单臂小样本研究，期待更大样本的III期验证结果。 04 总结与展望随着PANOVA-3数据公布，局部晚期胰腺癌患者首次迎来生存期与生存质量的双重突破。期望在真实世界中，能够验证其疗效和安全性。 ★

ASCO会议临床3期临床结果申请上市

2025-08-20

·癌度

《癌度快报》2025年8月20日

临床试验病友交流群（点击）一、新药快讯 1、免疫治疗双子星伊匹单抗与纳武利尤单抗治疗胶质母细胞瘤失利胶质母细胞瘤是最常见的脑癌，放疗与替莫唑胺化疗是标准治疗方案，搭配肿瘤电场治疗则会让患者获益，最近的一项研究探索在新诊断的占比60%的MGMT启动子未甲基化的胶质瘤，通过放疗联合双免疫治疗药物伊匹木单抗和纳武利尤单抗，对比放疗联合替莫唑胺的疗效差异。结果试验组的中位无进展生存时间为7.7个月，显著比对照组的8.5个月要低，两组患者的中位总生存时间都是13个月，因此免疫治疗双子星在新诊断的胶质母细胞瘤失利，不比标准治疗方案更好。 2、靶向药氟泽雷赛治疗KRAS基因G12C突变肠癌展现良好疗效近期，浙江大学医学院附属第二医院发布的一项研究表明，代号为IBI351的靶向药氟泽雷赛单药治疗KRAS基因G12C突变的肠癌展现不错的疗效，总体的治疗应答率为44.6%，中位无进展生存时间达到了8.1个月，中位总生存时间是17个月；对于接受过至少两线既往治疗的患者，治疗应答率达到了63%，中位无进展生存时间为8.2个月，这款靶向药对KRAS基因突变的肠癌总体疗效不错。 3、B7-H3抗体偶联药I-DXd治疗广泛期小细胞肺癌获得突破疗法认定近日，美国食品药品监督管理局FDA授予抗体偶联药I-DXd突破性疗法认定，用于治疗广泛期小细胞肺癌。这款药的靶点是B7-H3，目前公布的临床试验证据表明，对于接受1到3次治疗的广泛期小细胞肺癌，该药的治疗应答率达到了54.8%，疾病控制率达到了90.5%，在脑转移的患者中，61.1%的患者肿瘤大幅度缩小或完全消失。后面的临床试验该药将探索头颈癌、食管癌、非小细胞肺癌、肉瘤等实体瘤治疗的效果。二、抗癌前沿 1、肺癌的MRD基因检测，需要谨慎和理性选择肺癌的治疗里有一种基因检测叫做微小可测量残留病灶（MRD）成为热门话题，这种检测的原理是血液里肿瘤细胞释放的循环肿瘤DNA，如血液里的癌细胞的基因信息能被检测到，那就证明手术没有切除干净还有残留。但MRD需要首次检测肿瘤组织几百个上千个基因，持续2年不断进行血液样本基因检测才能更好发现肿瘤复发线索，这就导致基因检测费用较高。对于手术后已经确定完全治愈的患者没必要做MRD，术后复发风险很低的肺癌，如磨玻璃为主型的肺腺癌、病灶很小且分化比较高的肺癌也不需要测。多原发肺癌可以慎重考虑。

突破性疗法免疫疗法

2025-08-19

·BioArt

Cancer Cell | 卞修武/冯华/陈图南/李飞/王玉海合作在环路层面解析远距离胆碱能输入对GBM进展的影响

胶质母细胞瘤（glioblastoma,GBM）是最常见的原发性恶性脑肿瘤，5年生存率远低于10%，大多数患者死于诊断后2年以内，属于“癌症之王”之一。GBM的高度侵袭主要局限于中枢神经系统内，这凸显了“神经环境”对其生存和进展的关键作用。最新研究显示，GBM作为神经环路的积极参与者，胶质瘤细胞与神经元进行复杂的相互作用来促进肿瘤生长【1,2】。比如，神经元能够通过“突触”连接和旁分泌效应（Neuroligin-3, BDNF，IGF-1等）促进GBM进展【3-6】，GBM也能诱导邻近神经元的高兴奋性导致癫痫发生【7】。然而，神经元-胶质瘤细胞全脑连接网络，特别是与远距离神经元和多种神经递质系统的连接及对胶质瘤的影响，目前仍知之甚少。 2025年8月18日，来自陆军军医大学（第三军医大学）西南医院脑胶质瘤医学研究中心卞修武院士团队（病理科）联合冯华教授团队（神经外科）和无锡第904医院神经外科王玉海教授，合作在Cancer Cell杂志在线发表了题为Long-range Cholinergic Input Promotes Glioblastoma Progression的研究论文。在绘制神经元-胶质瘤细胞全脑连接图谱的基础上，团队首次在环路层面系统揭示了远距离胆碱能神经元调控对GBM进展的影响，以及不同神经递质对GBM进展的作用与机制，并发现东莨菪碱抗GBM作用（“老药新用”），同时警示乙酰胆碱酯酶抑制剂可能具有加速GBM进展的风险，为“癌症神经科学”（Cancer Neuroscience）提供了崭新认识和研究范式。 1. 绘制神经元-胶质瘤细胞全脑连接图谱，以及胆碱能神经元与胶质瘤细胞之间“突触”鉴定为解析神经元与胶质瘤细胞的全脑连接网络，研究团队构建了基于伪狂犬病毒（Rabies virus）的逆行跨单突触示踪技术平台，结合荧光显微光学切片断层成像（fMOST）和原位杂交技术，系统分析了种植于不同脑区、具有不同分子分型的原代人源胶质瘤细胞的上游神经元在全脑的分布特征及其亚型。研究不仅确认了已被广泛研究的胶质瘤细胞周围的兴奋性神经元连接，而且发现胶质瘤细胞能与分布于全脑范围的远距离神经调质神经元建立广泛连接。这些关键的上游神经元包括：基底前脑的胆碱能（ChAT）神经元、中缝背核的5-羟色胺能（5-HT）神经元、蓝斑核的去甲肾上腺素能（NA）神经元以及黑质的多巴胺能（DA）神经元。进一步研究发现，种植在不同脑区的胶质瘤细胞均能高效地与胆碱能（ChAT）神经元建立连接，其连接数量仅次于兴奋性神经元。尤为重要的是，利用免疫电镜技术，研究团队在超微结构水平证实，基底前脑布罗卡斜带核（DBB）的ChAT神经元（DBBChAT）能与前额叶移植的胶质瘤细胞形成典型的“突触”结构。功能实验显示，光遗传学特异性激活DBBChAT纤维末梢可有效诱导胶质瘤细胞产生钙信号活动，直接证明了这种连接的功能性。 2. 首次从环路层面解析远距离胆碱能神经元通过CHRM3促进了GBM进展研究团队运用多种神经环路调控技术深入探究了DBBChAT神经元对胶质瘤进展的作用与机制。结果显示，特异性杀死或抑制DBBChAT神经元活性，或阻断/消除其释放的乙酰胆碱（ACh），均能显著抑制GBM细胞的增殖。然而，化学遗传学激活DBBChAT神经元显著促进了GBM细胞增殖。基于单细胞转录组测序和CRISPR-Cas9无差别筛选，鉴定出毒蕈碱型乙酰胆碱受体M3（CHRM3）是介导乙酰胆碱促GBM细胞增殖效应的关键分子。 3. 揭示不同神经递质对GBM细胞的差异性作用与机制（谷氨酸vs乙酰胆碱）为了对比不同神经递质对GBM细胞的影响与机制，我们选择与GBM细胞建立连接最多的两种神经元：谷氨酸能神经元vs胆碱能神经元。利用钙成像、测序及活体成像等实验，发现CHRM3受体激活对GBM钙信号、增殖相关pathway的促进作用更为持久。有意思的是，联合阻断两种受体在抗GBM中获得叠加效应。 4. 胶质瘤治疗新发现：东莨菪碱“老药新用”增效，乙酰胆碱酯酶抑制剂需警惕风险，为临床决策提供了新依据在临床应用探索方面，研究团队发现临床常用药物、具有“老药新用”潜力的M受体抑制剂东莨菪碱，在胶质瘤模型小鼠中能够抑制GBM进展，并增强替莫唑胺的化疗效果。然而，研究同时提示，常用乙酰胆碱酯酶抑制剂多奈哌齐可能加速GBM进展，这提示临床需重新评估此类药物在胶质瘤患者中的用药风险。值得注意的是，该研究的发现与近期来自国际不同顶尖独立实验室的研究结果一致、相互印证（海德堡大学Varun Venkataramani实验室论文：Svenja K Tetzlaff et al. Cell, 2025【8】; 宾夕法尼亚大学Hongjun Song实验室论文：Yusha Sun et al. Nature, 2025【9】; 斯坦福大学Michelle Monje实验室论文：Richard Drexler et al. Cell, 2025【10】）。这种不谋而合的现象，充分证明了该论文研究方法和结论的可靠性，以及胆碱能神经元调控在胶质瘤进展中的关键作用。即使如此，该研究依旧保持了多个独立发现：（1）提供了首个环路水平胆碱能远程调控对GBM影响的证据；（2）揭示了不同神经递质（ACh vs Glu）对GBM细胞的作用与机制差异；（3）发现了东莨菪碱“老药新用”抗GBM作用，以及乙酰胆碱酯酶抑制剂可能加速GBM进展。西南医院病理科博士后杨阳副教授（合作导师卞修武院士）、神经外科杨川艳实验师和重庆市公共卫生医疗救治中心病理科陈雪竹技师为该论文共同第一作者。西南医院病理科卞修武院士、西南医院神经外科冯华教授/陈图南副教授/李飞教授、无锡904医院神经外科王玉海教授为共同通讯作者。原文链接： https://doi.org/10.1016/j.ccell.2025.07.024 制版人：十一参考文献 1.De Silva, M.I., B.W. Stringer and C. Bardy, Neuronal and tumourigenic boundaries of glioblastoma plasticity. Trends in Cancer, 2022. 2.Winkler, F., et al., Cancer neuroscience: State of the field, emerging directions. Cell, 2023. 186(8): p. 1689-1707. 3.Venkataramani, V., et al., Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature, 2019. 4.Venkatesh, H.S., et al., Electrical and synaptic integration of glioma into neural circuits. Nature, 2019. 5.Venkatesh, H.S., et al., Neuronal Activity Promotes Glioma Growth through Neuroligin-3 Secretion. Cell, 2015. 161(4): p. 803-816. 6.Chen, P., et al., Olfactory sensory experience regulates gliomagenesis via neuronal IGF1. Nature, 2022. 606(7914): p. 550-556. 7.Zhang, Y., et al., Potassium ion channel modulation at cancer-neural interface enhances neuronal excitability in epileptogenic glioblastoma multiforme. Neuron, 2025. 113(2): p. 225-243.e10. 8.Tetzlaff, S.K., et al., Characterizing and targeting glioblastoma neuron-tumor networks with retrograde tracing. Cell, 2025. 188(2): p. 390-411.e36. 9.Sun, Y., et al., Brain-wide neuronal circuit connectome of human glioblastoma. Nature, 2025. 641(8061): p. 222-231. 10.Drexler, R., et al., Cholinergic neuronal activity promotes diffuse midline glioma growth through muscarinic signaling. Cell, 2025. （可上下滑动阅览）学术合作组织（*排名不分先后）战略合作伙伴（*排名不分先后） · 转载须知【非原创文章】本文著作权归文章作者所有，欢迎个人转发分享，未经作者的允许禁止转载，作者拥有所有法定权利，违者必究。 BioArt Med Plants 人才招聘近期直播推荐点击主页推荐活动关注更多最新活动！

100 项与替莫唑胺相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D06067	替莫唑胺	L01AX03	DB00853

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
尤文肉瘤	日本	Ohara Pharmaceutical Co., Ltd.	2019-02-21
尤文肉瘤	日本	MSD KK (Tokyo)	2019-02-21
脑恶性胶质瘤	欧盟	Teva Pharmaceuticals Europe BV	2010-01-28
脑恶性胶质瘤	冰岛	Teva Pharmaceuticals Europe BV	2010-01-28
脑恶性胶质瘤	列支敦士登	Teva Pharmaceuticals Europe BV	2010-01-28
脑恶性胶质瘤	挪威	Teva Pharmaceuticals Europe BV	2010-01-28
转移性恶性黑色素瘤	澳大利亚	Merck Sharp & Dohme (Australia) Pty Ltd.	2009-11-13
胶质母细胞瘤	中国	江苏天士力帝益药业有限公司	2004-04-30
星形细胞瘤	欧盟	Merck Sharp & Dohme BV	1999-01-26
星形细胞瘤	冰岛	Merck Sharp & Dohme BV	1999-01-26
星形细胞瘤	列支敦士登	Merck Sharp & Dohme BV	1999-01-26
星形细胞瘤	挪威	Merck Sharp & Dohme BV	1999-01-26
多形性胶质母细胞瘤	欧盟	Merck Sharp & Dohme BV	1999-01-26
多形性胶质母细胞瘤	冰岛	Merck Sharp & Dohme BV	1999-01-26
多形性胶质母细胞瘤	列支敦士登	Merck Sharp & Dohme BV	1999-01-26
多形性胶质母细胞瘤	挪威	Merck Sharp & Dohme BV	1999-01-26
胶质瘤	欧盟	Merck Sharp & Dohme BV	1999-01-26
胶质瘤	冰岛	Merck Sharp & Dohme BV	1999-01-26
胶质瘤	列支敦士登	Merck Sharp & Dohme BV	1999-01-26
胶质瘤	挪威	Merck Sharp & Dohme BV	1999-01-26

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
神经母细胞瘤	申请上市	欧盟	ORPHELIA Pharma SAS	2024-11-14
子宫平滑肌肉瘤	临床3期	美国	Alliance for Clinical Trials in Oncology	2022-03-30
脑干胶质瘤	临床3期	美国	National Cancer Institute	2011-01-26
脑干胶质瘤	临床3期	加拿大	National Cancer Institute	2011-01-26
成人脑星形细胞瘤	临床3期	美国	National Cancer Institute	2011-01-26
成人脑星形细胞瘤	临床3期	加拿大	National Cancer Institute	2011-01-26
高级别胶质瘤	临床3期	美国	National Cancer Institute	2011-01-26
高级别胶质瘤	临床3期	加拿大	National Cancer Institute	2011-01-26
小儿小脑星形细胞瘤	临床3期	美国	National Cancer Institute	2011-01-26
小儿小脑星形细胞瘤	临床3期	加拿大	National Cancer Institute	2011-01-26

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03137888 (CTgov)	临床2期	神经胶质肉瘤 \| 胶质母细胞瘤	30	Spectroscopic Magnetic Resonance Imaging+Temozolomide	糧觸壓願淵鹽繭範襯夢 = 蓋範廠願襯繭網繭襯獵獵構衊淵夢襯鬱簾廠築 (淵顧範壓醖鏇鹽鏇顧憲, 觸膚鹽獵窪觸簾膚鹽膚 ~ 構鬱製膚選醖簾網網簾) 更多	-	2025-08-03
NCT04574856 (Phase 2 Study of Multiparametric Magnetic Resonance Imaging-Guided High-Dose Response-Adaptive Radiation Therapy With Concurrent Temozolomide in Patients With Newly Diagnosed Glioblastoma, Pubmed \| Int J Radiat Oncol Biol Phys)	临床2期	胶质母细胞瘤	30	Temozolomide (Patients with newly diagnosed GBM)	衊鹹網獵製顧膚網鏇餘(積餘膚鹹構蓋鏇廠獵構) = 餘衊簾繭襯膚簾遞襯齋鹹鏇鏇齋積獵遞鏇夢鹽 (顧鏇製襯窪憲齋醖獵憲 ) 更多	积极	2025-07-01
NCT00629343 (CTgov)	临床1期	恶性间皮瘤 \| 软组织肉瘤	27	Temozolomide+Azacitidine	鏇顧鏇範窪鏇蓋夢壓網 = 憲憲鬱憲壓齋鹹蓋願鬱鹽窪憲鏇簾廠觸餘醖憲 (製鏇蓋顧繭繭簾壓築獵, 衊衊夢鹽網鬱製糧觸範 ~ 構艱網繭選夢膚襯襯醖) 更多	-	2025-06-05
ASCO2025	N/A	平滑肌肉瘤维持	20	Doxorubicin plus dacarbazine	壓廠鹽顧鬱窪繭餘網衊(鹽醖醖窪製艱衊艱鹽築) = 鏇夢衊積鑰鏇壓艱蓋願築鏇窪蓋鑰積鹽製製繭 (製糧觸齋淵獵窪廠構膚 )	积极	2025-05-30
NCT04280848 (Phase II study of UCPVax in newly diagnosed glioblastoma, ASCO2025)	临床2期	胶质母细胞瘤辅助 non-mutated IDH1 \| unmethylated MGMT status	-	UCPVax + Temozolomide	獵範膚夢網衊選糧蓋壓(艱淵廠鹹選蓋蓋襯廠憲) = 鏇鬱範網壓鹹壓鏇繭鹹壓鏇觸艱齋餘選餘繭鏇 (製獵範選餘願觸夢範簾 ) 更多	积极	2025-05-30
NCT00626990 (CATNON, ASCO2025)	临床3期	胶质瘤辅助 IDH mutation \| total copy number alterations \| methylation subtype	751	Radiotherapy alone	遞獵齋襯願範糧鏇蓋艱(觸鏇淵簾鬱顧遞繭積餘) = 8.5 years 衊觸鏇鏇廠齋顧餘選衊 (廠蓋積齋積糧窪齋鏇顧 ) 更多	积极	2025-05-30
				Concurrent Temozolomide
BT008 (ASCO2025)	临床1/2期	高级别胶质瘤辅助	34	temozolomideTMZde (MB-FUS+TMZ)	獵廠簾壓積淵構衊遞網(淵齋鹽製鹽鏇繭膚構積) = No serious procedure-related AEs were seen, with the most common AEs being mild, self-resolving 範蓋齋蓋鬱觸鹹鏇廠襯 (糧醖窪蓋醖構蓋糧鹹構 ) 更多	积极	2025-05-30
				temozolomide (External cohort)
ASCO2025	N/A	-	159	temozolomide (Pancreatic NETs (PNETs))	憲鑰選窪廠餘顧選壓鹽(膚憲選蓋鹹鹽積選鹽製) = 願鹹鬱廠糧積獵獵觸鹽鹽糧範網窪獵遞齋築鹹 (蓋網鬱鏇網製製鹽壓鬱 ) 更多	积极	2025-05-30
				temozolomide (Gastrointestinal NETs (GINETs))	憲鑰選窪廠餘顧選壓鹽(膚憲選蓋鹹鹽積選鹽製) = 繭遞遞糧繭憲構網願蓋鹽糧範網窪獵遞齋築鹹 (蓋網鬱鏇網製製鹽壓鬱 ) 更多
NCT02761070 (JCOG1308C, ASCO2025)	临床3期	复发性胶质母细胞瘤	146	Bevacizumab	窪齋積製範齋鹹憲窪壓(願憲製顧膚衊鑰壓窪製) = 19.4% in arm A 製選壓壓簾鏇願蓋製構 (觸選襯廠選齋觸齋積衊 ) 更多	不佳	2025-05-30
				Dose-dense Temozolomide
ASCO2025	临床2期	高风险神经母细胞瘤	34	HITS (Irinotecan, Temozolomide, Naxitamab, GM-CSF)	糧選選壓憲築遞鹹衊糧(範積鏇蓋鏇獵廠遞顧遞) = 鏇獵餘艱鹽鹹鑰選窪廠壓艱膚鑰觸鹽壓壓膚醖 (壓廠廠蓋鹽醖艱繭壓顧 ) 更多	积极	2025-05-30
				NICE (Naxitamab, GM-CSF, Ifosfamide, Carboplatin, Etoposide)	糧選選壓憲築遞鹹衊糧(範積鏇蓋鏇獵廠遞顧遞) = 鏇鑰醖鏇餘選網襯窪簾壓艱膚鑰觸鹽壓壓膚醖 (壓廠廠蓋鹽醖艱繭壓顧 ) 更多