Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Pfizer Inc., New York City, NY, USA.
Nat Med. 2021 Aug;27(8):1345-1356. doi: 10.1038/s41591-021-01450-2. Epub 2021 Aug 12.
Worldwide, lung cancer is the most common cause of cancer-related deaths. Molecular targeted therapies and immunotherapies for non-small-cell lung cancer (NSCLC) have improved outcomes markedly over the past two decades. However, the vast majority of advanced NSCLCs become resistant to current treatments and eventually progress. In this Perspective, we discuss some of the recent breakthrough therapies developed for NSCLC, focusing on immunotherapies and targeted therapies. We highlight our current understanding of mechanisms of resistance and the importance of incorporating genomic analyses into clinical studies to decipher these further. We underscore the future role of neoadjuvant and maintenance combination therapy approaches to potentially cure early disease. A major challenge to successful development of rational combination therapies will be the application of robust predictive biomarkers for clear-cut patient stratification, and we provide our views on clinical research areas that could influence how NSCLC will be managed over the coming decade.
在全球范围内，肺癌是癌症相关死亡的最常见原因。过去二十年来，针对非小细胞肺癌（NSCLC）的分子靶向治疗和免疫疗法显著改善了治疗效果。然而，绝大多数晚期 NSCLC 会对当前的治疗产生耐药性，最终病情进展。在本观点中，我们讨论了最近为 NSCLC 开发的一些突破性疗法，重点介绍了免疫疗法和靶向疗法。我们强调了我们对耐药机制的现有理解，以及将基因组分析纳入临床研究以进一步阐明这些机制的重要性。我们强调了新辅助和维持联合治疗方法在早期疾病治愈方面的未来作用。成功开发合理联合疗法的主要挑战将是应用稳健的预测生物标志物来明确患者分层，我们就可能影响未来十年 NSCLC 管理方式的临床研究领域提供了我们的观点。
