结直肠癌中对表皮生长因子受体（EGFR）靶向治疗耐药的机制：不止于遗传学。
Mechanisms of resistance to EGFR-targeted therapies in colorectal cancer: more than just genetics.
作者信息
Parseghian Christine, Eluri Madhulika, Kopetz Scott, Raghav Kanwal
机构信息
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
出版信息
Front Cell Dev Biol. 2023 Sep 15;11:1176657. doi: 10.3389/fcell.2023.1176657. eCollection 2023.
Abstract
The development of acquired resistance to anti-EGFR therapies remains poorly understood, with most research to date exploring, and trying to overcome, various genomic mechanisms of resistance. However, recent work supports a model of resistance whereby transcriptomic mechanisms of resistance predominate in the presence of active cytotoxic chemotherapy combined with anti-EGFR therapy in the first-line setting, with a greater predominance of acquired MAPK mutations after single-agent anti-EGFR therapy in the later-line setting. The proposed model has implications for prospective studies evaluating anti-EGFR rechallenge strategies guided by acquired MAPK mutations and highlights the need to address transcriptional mechanisms of resistance.
摘要
对抗表皮生长因子受体（EGFR）疗法获得性耐药的发展仍知之甚少，迄今为止，大多数研究都在探索并试图克服各种耐药的基因组机制。然而，最近的研究支持一种耐药模型，即在一线治疗中，当活性细胞毒性化疗与抗EGFR疗法联合使用时，耐药的转录组机制占主导地位，而在二线治疗中，单药抗EGFR疗法后获得性丝裂原活化蛋白激酶（MAPK）突变更为普遍。所提出的模型对评估由获得性MAPK突变指导的抗EGFR再挑战策略的前瞻性研究具有启示意义，并强调了解决耐药转录机制的必要性。
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