Pathak A, Rajappa S, Gore A
Department of Oncology, Cancer Care Clinic and Hospital, Nagpur, India.
Indo-American Cancer Institute and Research Centre, Hyderabad, Telangana, India.
Indian J Cancer. 2017 Dec;54(Supplement):S1-S8. doi: 10.4103/ijc.IJC_505_17.
Nonsmall cell lung cancer (NSCLC) is increasingly being treated with targeted therapies. Epidermal growth factor receptor (EGFR) has been extensively studied in NSCLC as an oncogenic driver. However, the efficacy of the EGFR tyrosine kinase inhibitors (TKIs) is adversely impacted by the development of resistance. The occurrence of de novo resistance to EGFR TKIs is attributed to multiple mechanisms such as point mutations of oncogenes and chromosomal rearrangements. The development of acquired resistance to EGFR TKIs is facilitated by secondary mutations, phenotypical transformation, aberrance of downstream pathways, and activation of alternate signaling pathways. The T790M mutation is the most common mutation that accounts for about half of the acquired resistance to EGFR TKIs. This review article provides an overview of the common oncogenic drivers, targeted therapies for NSCLC, and the established mechanisms implicated in the development of resistance to the EGFR TKIs.
非小细胞肺癌（NSCLC）越来越多地采用靶向治疗。表皮生长因子受体（EGFR）作为一种致癌驱动因子，在NSCLC中已得到广泛研究。然而，EGFR酪氨酸激酶抑制剂（TKIs）的疗效会受到耐药性发展的不利影响。对EGFR TKIs的原发性耐药的发生归因于多种机制，如癌基因的点突变和染色体重排。EGFR TKIs获得性耐药的发展是由继发性突变、表型转化、下游通路异常以及替代信号通路激活所促成的。T790M突变是最常见的突变，约占EGFR TKIs获得性耐药的一半。这篇综述文章概述了常见的致癌驱动因子、NSCLC的靶向治疗以及与EGFR TKIs耐药性发展相关的既定机制。
