Boilève Alice, Smolenschi Cristina, Lambert Aurélien, Boige Valérie, Delaye Matthieu, Camilleri Géraldine M, Tarabay Anthony, Valéry Marine, Fuerea Alina, Pudlarz Thomas, Mathieu Jacques R R, Jaulin Fanny, Hollebecque Antoine, Ducreux Michel
Gustave Roussy, Département de Médecine Oncologique, 94805 Villejuif, France.
Université Paris-Saclay, 91400 Orsay, France.
Cancers (Basel). 2024 Oct 12;16(20):3455. doi: 10.3390/cancers16203455.
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, with significant public health concerns. This review examines the landscape of KRAS inhibition in colorectal cancer (CRC), focusing on recent advances in therapeutic strategies targeting this oncogene. Historically deemed undruggable due to its complex structure and essential role in tumorigenesis, mutations are prevalent in CRC and are associated with poor prognosis. However, breakthroughs in drug development have led to the emergence of KRAS inhibitors as promising treatment options. This review discusses various classes of KRAS inhibitors, including covalent and non-covalent inhibitors, as well as combination therapies aimed at enhancing efficacy and overcoming resistance mechanisms. It highlights recent clinical trials evaluating the efficacy of KRAS inhibitors either as monotherapy or in combination with other agents, such as anti-EGFR antibodies. Despite challenges such as resistance mechanisms and tumor heterogeneity, the development of KRAS inhibitors represents a significant advance in CRC treatment and holds promise for improving patient outcomes in the future.
结直肠癌(CRC)仍然是全球癌症相关死亡的主要原因,引起了重大的公共卫生关注。本综述探讨了结直肠癌(CRC)中KRAS抑制的情况,重点关注靶向该致癌基因的治疗策略的最新进展。由于其复杂的结构和在肿瘤发生中的重要作用,KRAS历史上被认为是不可成药的,但KRAS突变在CRC中很普遍,且与预后不良相关。然而,药物开发的突破导致了KRAS抑制剂作为有前景的治疗选择的出现。本综述讨论了各类KRAS抑制剂,包括共价和非共价抑制剂,以及旨在提高疗效和克服耐药机制的联合疗法。它强调了最近评估KRAS抑制剂作为单一疗法或与其他药物(如抗EGFR抗体)联合使用的疗效的临床试验。尽管存在耐药机制和肿瘤异质性等挑战,但KRAS抑制剂的开发代表了CRC治疗的重大进展,并有望在未来改善患者的预后。