Qunaj Lindor, May Michael S, Neugut Alfred I, Herzberg Benjamin O
Division of Hematology and Oncology, Department of Medicine, Columbia University, New York, NY, United States.
Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, United States.
Front Oncol. 2023 Sep 15;13:1252516. doi: 10.3389/fonc.2023.1252516. eCollection 2023.
G12C mutations are critical in the pathogenesis of multiple cancer types, including non-small cell lung (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and colorectal (CRC) cancers. As such, they have increasingly become a target of novel therapies in the management of these malignancies. However, the therapeutic success of KRAS G12C inhibitors to date has been far more limited in CRC and PDAC than NSCLC. In this review, we briefly summarize the biochemistry of targeting and treatment resistance, highlight differences in the epidemiology of various G12C-mutated cancers, and provide an overview of the published data on KRAS G12C inhibitors for various indications. We conclude with a summary of ongoing clinical trials in G12C-mutant CRC and a discussion of future directions in the management of this disease. G12C mutation, targeted therapies, colorectal cancer, non-small cell lung cancer, pancreatic cancer, drug development.
G12C突变在多种癌症类型的发病机制中至关重要，包括非小细胞肺癌（NSCLC）、胰腺导管腺癌（PDAC）和结直肠癌（CRC）。因此，它们越来越成为这些恶性肿瘤治疗新疗法的靶点。然而，迄今为止，KRAS G12C抑制剂在CRC和PDAC中的治疗成功远比在NSCLC中有限。在这篇综述中，我们简要总结了靶向治疗和治疗耐药的生物化学机制，强调了各种G12C突变癌症流行病学的差异，并概述了已发表的关于KRAS G12C抑制剂用于各种适应症的数据。我们最后总结了G12C突变CRC正在进行的临床试验，并讨论了该疾病治疗的未来方向。G12C突变、靶向治疗、结直肠癌、非小细胞肺癌、胰腺癌、药物研发
