Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610041, China.
Pharmacol Res. 2024 Aug;206:107304. doi: 10.1016/j.phrs.2024.107304. Epub 2024 Jul 11.
Over the last decade, epidermal growth factor receptor (EGFR)-targeted therapies have transformed the treatment landscape for patients with advanced solid tumors. Despite these advances, resistance to anti-EGFR therapies is still a significant clinical challenge. While cell-autonomous mechanisms of resistance are well-documented, they do not fully elucidate the complexity of drug resistance. Cancer-associated fibroblasts (CAFs), key mediators within the tumor microenvironment (TME), have emerged as pivotal players in cancer progression and chemoresistance. Recent evidence implicates CAFs in resistance to anti-EGFR therapies, suggesting they may undermine treatment efficacy. This review synthesizes current data, highlighting the critical role of CAFs in resistance pathogenesis and summarizing recent therapeutic strategies targeting CAFs. We underscore the challenges and advocate for the exploration of CAFs as a potential dual-targeted approach.
在过去的十年中，表皮生长因子受体（EGFR）靶向治疗已经改变了晚期实体瘤患者的治疗格局。尽管取得了这些进展，但对 EGFR 靶向治疗的耐药性仍然是一个重大的临床挑战。虽然细胞自主耐药机制已经有了详细的记录，但它们并没有完全阐明耐药性的复杂性。癌症相关成纤维细胞（CAFs）是肿瘤微环境（TME）中的关键介质，它们已成为癌症进展和化疗耐药的关键因素。最近的证据表明 CAFs 与抗 EGFR 治疗的耐药性有关，这表明它们可能会降低治疗效果。这篇综述综合了目前的数据，强调了 CAFs 在耐药发病机制中的关键作用，并总结了最近针对 CAFs 的治疗策略。我们强调了挑战，并主张将 CAFs 作为一种潜在的双重靶向治疗方法进行探索。
