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Abstract：
Kirsten rat sarcoma virus (KRAS) is the most frequently found oncogene in human cancers, including non-small-cell lung cancer (NSCLC). For many years, KRAS was considered \"undruggable\" due to its structure and difficult targeting. However, the discovery of the switch II region in the KRAS-G12C-mutated protein has changed the therapeutic landscape with the design and development of novel direct KRAS-G12C inhibitors. Sotorasib and adagrasib are FDA-approved targeted agents for pre-treated patients with KRAS-G12C-mutated NSCLC. Despite promising results, the efficacy of these novel inhibitors is limited by mechanisms of resistance. Ongoing studies are evaluating combination strategies for overcoming resistance. In this review, we summarize the biology of the KRAS protein and the characteristics of KRAS mutations. We then present current and emerging therapeutic approaches for targeting KRAS mutation subtypes intending to provide individualized treatment for lung cancer harboring this challenging driver mutation.
摘要：
Kirsten大鼠肉瘤病毒（KRAS）是人类癌症中最常见的癌基因，包括非小细胞肺癌（NSCLC）。多年来,由于其结构和难以定位，KRAS被认为是“不可用的”。然而,KRAS-G12C突变蛋白中开关II区的发现,随着新型直接KRAS-G12C抑制剂的设计和开发,改变了治疗领域.Sotorasib和adagrasib是FDA批准的靶向药物，用于KRAS-G12C突变的NSCLC患者。尽管结果很有希望，这些新型抑制剂的功效受到耐药机制的限制。正在进行的研究正在评估克服阻力的组合策略。在这次审查中,我们总结了KRAS蛋白的生物学特性和KRAS突变的特点。然后，我们提出了针对KRAS突变亚型的当前和新兴治疗方法，旨在为具有这种挑战性的驱动突变的肺癌提供个性化治疗。
