Filis Panagiotis, Salgkamis Dimitrios, Matikas Alexios, Zerdes Ioannis
Department of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, 451 10 Ioannina, Greece.
Department of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden.
Drug Discov Today. 2025 Jan;30(1):104250. doi: 10.1016/j.drudis.2024.104250. Epub 2024 Nov 24.
The multi-selective tri-complex RAS(ON) inhibitors RMC-7977 and RMC-6236 signal new avenues for RAS targeting. This systematic review aims to comprehensively present the available preclinical and early clinical data on these agents. We screened Medline, Scopus, the ESMO and ASCO conference sites and ClinicalTrials.gov for related studies and found four published preclinical studies and one clinical trial. In these reports, RMC-7977 and RMC-6236 effectively drove tumor suppression, especially in non-small cell lung cancer and pancreatic ductal adenocarcinoma, and minimal effects in healthy tissue were observed. MYC amplification was reported to be a main contributor to the development of resistance. Six trials are currently ongoing, including one randomized trial, and promising results are expected from combination with other agents, such as immune-checkpoint blockers.
多选择性三复合RAS（ON）抑制剂RMC-7977和RMC-6236为RAS靶向治疗开辟了新途径。本系统评价旨在全面展示这些药物的现有临床前和早期临床数据。我们在Medline、Scopus、ESMO和ASCO会议网站以及ClinicalTrials.gov上筛选相关研究，发现了四项已发表的临床前研究和一项临床试验。在这些报告中，RMC-7977和RMC-6236有效地促进了肿瘤抑制，尤其是在非小细胞肺癌和胰腺导管腺癌中，并且在健康组织中观察到的影响最小。据报道，MYC扩增是耐药性产生的主要原因。目前正在进行六项试验，包括一项随机试验，预计与其他药物（如免疫检查点阻滞剂）联合使用会取得有前景的结果。
