西妥昔单抗治疗转移性结直肠癌耐药机制的研究进展

Research progress on the mechanisms of drug resistance to cetuximab treatment in metastatic colorectal cancer

许建江 ¹刘涛 ¹王旭 ¹马明礼 ¹姜雷²

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作者信息

1. 兰州大学第一临床医学院兰州市730000
2. 兰州大学第一临床医学院兰州市730000;兰州大学第一医院普外科院兰州市730000
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摘要

西妥昔单抗是一种针对表皮生长因子受体(epidermal growth factor receptor,EGFR)的单克隆抗体(monoclonal antibody,mAb),应用于治疗转移性结直肠癌(metastatic colorectal cancer,mCRC).然而,大多数接受西妥昔单抗治疗的患者会因出现继发性耐药而导致疾病进展,耐药是西妥昔单抗治疗中面临的严峻挑战.西妥昔单抗的耐药机制不仅与RAS/RAF/PIK3CA基因突变相关,还与PI3K/AKT/mTOR、Wnt/β-catenin、c-MET/HGF以及RAS-MAPK等信号通路的异常激活密切相关.此外,HER2和MET扩增、微卫星不稳定、肿瘤代谢的改变及肿瘤微环境的变化等因素也可能导致患者对西妥昔单抗产生耐药.本文就西妥昔单抗治疗mCRC过程中耐药的潜在分子机制进行综述,以期为临床克服西妥昔单抗耐药提供新的思路.

Abstract

Cetuximab is a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR) for the treatment of metastat-ic colorectal cancer (mCRC). However,most patients treated with cetuximab experience disease progression due to the development of sec-ondary drug resistance,presenting a significant challenge in managing cetuximab therapy. Existing studies have found that cetuximab resist-ance mechanisms are not only linked to the RAS/RAF/PIK3CA genetic mutations but also closely associated with the abnormal activation of PI3K/AKT/mTOR,Wnt/β-catenin,c-MET/HGF,and RAS-MAPK signaling pathways. Additionally,HER2 and MET amplification,microsatellite instability,changes in tumor metabolism,and alterations in the tumor microenvironment may also contribute to cetuximab resistance in pa-tients. This review focuses on the potential molecular mechanisms of cetuximab resistance in the treatment of mCRC,and provides new ideas for overcoming cetuximab resistance in clinic.

关键词

转移性结直肠癌/表皮生长因子受体/西妥昔单抗/耐药性

Key words

metastatic colorectal cancer (mCRC)/epidermal growth factor receptor (EGFR)/cetuximab/drug resistance

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出版年

2024

中国肿瘤临床

中国抗癌协会

中国肿瘤临床

CSTPCD北大核心

影响因子：1.32

ISSN：1000-8179

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