中国实用外科杂志 ›› 2024, Vol. 44 ›› Issue (07): 774-780.DOI: 10.19538/j.cjps.issn1005-2208.2024.07.12

• 专题笔谈 • 上一篇    下一篇

结直肠癌靶向治疗的耐药机制及潜在解决方案

张    宏,卜嘉文   

  1. 中国医科大学附属盛京医院普通外科 结直肠肿瘤外科,辽宁沈阳110004
  • 出版日期:2024-07-01 发布日期:2024-07-21

  • Online:2024-07-01 Published:2024-07-21

摘要: 结直肠癌的耐药性与病人个体差异性和肿瘤细胞的异质性密切相关,其中耐药相关基因突变负荷的不同很大程度上决定了肿瘤靶向药物的治疗效果。表皮生长因子受体和血管内皮生长因子受体是目前结直肠癌靶向治疗研究最明确、开发相关药物最丰富的靶向治疗靶点。在过去的几十年里,结直肠癌的辅助治疗方式不断推陈出新。但在临床实践中,针对许多已证明的耐药靶点开发新型药物存在困难,且需要更加广泛的分子标记物来评估其靶向治疗的适应性及疗效。而高敏感度的基因组测序方法和不断进步的分子检测手段为探究结直肠癌的耐药机制和评估个性化分子的表达带来了极大的便利性。通过不断深入认知结直肠癌的耐药机制,有望探寻更多的结直肠癌靶向治疗位点,并且通过个体化评估不同病人的分子表达特征,为病人提供个体化的辅助治疗方案,改善晚期结直肠癌病人的预后。

关键词: 结直肠癌, 靶向治疗, 耐药, 表皮生长因子受体, 血管内皮生长因子受体

Abstract: The drug resistance of colorectal cancer is closely related to individual differences and the heterogeneity of tumor cells, among which the different mutation loads of drug resistance-related genes largely determine the therapeutic effect of tumor-targeted drugs. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are currently the clearest targets with the most diverse related drugs in the targeted therapy of colorectal cancer. In the past few decades, the adjuvant treatment methods for colorectal cancer have been constantly evolving. However, in clinical practice, there are difficulties in developing new drugs for many targets with well-proven drug resistance, and a wider range of molecular markers are needed to evaluate the adaptability and efficacy of targeted therapy. The highly sensitive genome sequencing methods and continuously improving molecular detection methods have brought great convenience to explore the drug resistance mechanism of colorectal cancer and evaluate the expression of personalized molecules. By continuously deepening the understanding of the drug resistance mechanism of colorectal cancer, it is expected to explore more targeted treatment loci for colorectal cancer and provide personalized adjunctive treatment plans for patients by individually evaluating the molecular expression characteristics of different patients, improving the prognosis of advanced colorectal cancer patients.

Key words: colorectal cancer, targeted therapy, drug resistance, epidermal growth factor receptor, vascular endothelial growth factor receptor