吉非替尼和厄洛替尼耐药机制

吉非替尼和厄洛替尼是首批用于晚期非小细胞肺癌(NSCLC)的分子靶向药物,尽管治疗效果显著,但最终多数患者均会发生耐药.近年来研究表明,其耐药机制与表皮生长因子受体(EGFR)二次突变、其他酪氨酸激酶家族受体异常活化及信号通路成分或调节因子基因表达的改变等有关.另有研究表明,可能与EGFR受体内化及肿瘤微环境改变也有相关性.进一步研究其耐药机制,并寻找克服或逆转耐药的方法、开发新的靶向药物已成为肺癌治疗领域的前沿课题.

Mechanisms of drug resistance to gefifinib and erlotinib

Gefitinib and erlotinib are the first generation of targeted therapeutic agents approved for the treatment of advanced non-small cell lung cancer. Despite a dramatic initial response, most patients subsequently and ultimately become resistant to the drugs. Recent studies have proposed various mechanisms of such resistance, some of which related to a second mutation in epidermal growth factor receptor, aberrant activation of other tyrosine kinase receptors, bypassing signal pathways and constitutive activation of downstream signal molecules. Other researches also associated the drug resistance to internalization of epidermal growth factor receptor and changes in tumor microenvironment. Furture studies need to focus on overcoming or reversing resistance to the drugs and developing new targeted therapeutic agents.