关键词: Anti-EGFR therapy Cancer-associated fibroblast Epidermal growth factor receptor Tumor microenvironment resistance

Mesh : Humans ErbB Receptors / antagonists & inhibitors metabolism Drug Resistance, Neoplasm Cancer-Associated Fibroblasts / drug effects metabolism Neoplasms / drug therapy metabolism pathology Animals Antineoplastic Agents / therapeutic use pharmacology Tumor Microenvironment / drug effects

来  源:   DOI:10.1016/j.phrs.2024.107304

Abstract:
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.
摘要:
在过去的十年里,表皮生长因子受体(EGFR)靶向治疗改变了晚期实体瘤患者的治疗前景.尽管取得了这些进展,抗EGFR治疗的耐药性仍然是一个重大的临床挑战.虽然细胞自主的抵抗机制是有据可查的,他们没有完全阐明耐药性的复杂性。癌症相关成纤维细胞(CAFs),肿瘤微环境(TME)内的关键介质,已经成为癌症进展和化疗耐药性的关键参与者。最近的证据表明CAFs对抗EGFR治疗耐药,这表明它们可能会破坏治疗效果。这篇综述综合了当前的数据,强调CAFs在耐药发病机制中的关键作用,并总结最近针对CAFs的治疗策略。我们强调挑战,并倡导探索CAF作为一种潜在的双目标方法。
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