Kumarakulasinghe Nesaretnam Barr, van Zanwijk Nico, Soo Ross A
Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore.
Respirology. 2015 Apr;20(3):370-8. doi: 10.1111/resp.12490. Epub 2015 Feb 17.
Historically, patients with advanced stage non-small cell lung cancer (NSCLC) were treated with chemotherapy alone, but a therapeutic plateau has been reached. Advances in the understanding of molecular genetics have led to the recognition of multiple molecularly distinct subsets of NSCLC. This in turn has led to the development of rationally directed molecular targeted therapy, leading to improved clinical outcomes. Tumour genotyping for EGFR mutations and ALK rearrangement has meant chemotherapy is no longer given automatically as first-line treatment but reserved for when patients do not have a 'druggable' driver oncogene. In this review, we will address the current status of clinically relevant driver mutations and emerging new molecular subsets in lung adenocarcinoma and squamous cell carcinoma, and the role of targeted therapy and mechanisms of acquired resistance to targeted therapy.
从历史上看，晚期非小细胞肺癌（NSCLC）患者仅接受化疗，但目前已达到治疗平台期。对分子遗传学认识的进展促使人们认识到NSCLC存在多个分子特征不同的亚组。这反过来又推动了合理导向的分子靶向治疗的发展，从而改善了临床结果。针对表皮生长因子受体（EGFR）突变和间变性淋巴瘤激酶（ALK）重排的肿瘤基因分型意味着化疗不再自动作为一线治疗，而是保留给没有“可靶向治疗”驱动癌基因的患者。在本综述中，我们将探讨肺腺癌和肺鳞状细胞癌中临床相关驱动突变和新兴新分子亚组的现状，以及靶向治疗的作用和获得性靶向治疗耐药机制。
