EGFR/TP53/RB1三重突变的小细胞肺癌转化研究及治疗进展

表皮生长因子受体（epidermal growth factor receptor，EGFR）突变型非小细胞肺癌（non-small cell lung cancer，NSCLC）患者在接受EGFR酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKIs ）靶向治疗后能获得临床获益，但之后会不可避免地出现获得性耐药，而发生小细胞肺癌（small cell lung cancer，SCLC）组织学转化被认为是一种罕见的耐药机制。随着二代基因检测（next- generation sequencing，NGS）技术的快速发展及广泛应用，研究者发现存在EGFR/TP53/RB1三重突变的NSCLC经靶向治疗后更容易发生SCLC组织学转化，并且转化型SCLC疗效及预后较差。本文对近年来关于EGFR突变的NSCLC发生SCLC组织学转化的研究作一综述，涉及相关的转化机制、可能有效的新型药物及治疗策略，为EGFR/TP53/RB1三重突变的转化型SCLC患者提供更多潜在的临床治疗选择。 

Advances in translational research and treatment of small cell lung cancer withEGFR/TP53/RB1 triple mutation

Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) have substantial clinical benefits after treatment with EGFR tyrosine kinase inhibitors (TKIs). However, acquired drug resistance is expected to inevitably develop, and histological transformation to small cell lung cancer (SCLC) is considered a rare mechanism of acquired drug resistance. Considering the wide application and rapid development of next-generation sequencing (NGS), researchers have found that the histological type of EGFR/TP53/RB1 triple mutation in NSCLC is more likely to transform into SCLC after completing targeted therapy. This is particularly worrisome because poor therapeutic efficacy and prognosis are crucial characteristics of transformed SCLC. Thus, in this review, recent studies on the histological transformation of SCLC in patients with EGFR-mutated NSCLC, including those on related transformation mechanisms and novel drugs and treatment strategies, were summarized to provide more potential treatment options for patients with EGFR/TP53/RB1 triple mutation-transformed SCLC.