Lung cancer is the leading cause of cancer-related deaths worldwide, highlighting a major clinical challenge. Lung cancer is broadly classified into two histologically distinct subtypes, termed small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). Identification of various oncogenic drivers of NSCLC has facilitated the development of targeted therapies that have dramatically improved patient outcomes. However, acquired resistance to these targeted therapies is common, which ultimately results in patient relapse. Several on-target and off-target resistance mechanisms have been described for targeted therapies in NSCLC. One common off-target mechanism of resistance to these therapies is histological transformation of the initial NSCLC into SCLC, a highly aggressive form of lung cancer that exhibits neuroendocrine histology. This mechanism of resistance presents a significant clinical challenge, since there are very few treatments available for these relapsed patients. Although the phenomenon of NSCLC-to-SCLC transformation was described almost 20 years ago, only recently have we begun to understand the mechanisms underlying this therapy-driven response. These recent discoveries will be key to identifying novel biomarkers and therapeutic strategies to improve outcomes of patients that undergo NSCLC-to-SCLC transformation. Here, we highlight these recent advances and discuss the potential therapeutic strategies that they have uncovered to target this mechanism of resistance.
肺癌是全球癌症相关死亡的首要原因，凸显出重大的临床挑战。肺癌在组织学上主要分为两种截然不同的亚型，即小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC）。对NSCLC多种致癌驱动因子的识别促进了靶向治疗的发展，显著改善了患者预后。然而，对这些靶向治疗产生获得性耐药的情况十分常见，最终导致患者疾病复发。目前已有研究描述了NSCLC靶向治疗中多种靶点内及脱靶耐药机制。其中一种常见的脱靶耐药机制是初始NSCLC组织学转化为SCLC——一种具有神经内分泌组织学特征的高度侵袭性肺癌。该耐药机制构成了严峻的临床挑战，因为针对这类复发患者的有效治疗方案极为有限。尽管NSCLC向SCLC转化的现象在近二十年前已被报道，但直到最近我们才开始理解这种治疗驱动反应的潜在机制。这些最新发现将成为识别新型生物标志物和开发治疗策略的关键，以改善经历NSCLC-SCLC转化患者的临床结局。本文重点阐述这些最新进展，并探讨其揭示的针对该耐药机制的潜在治疗策略。
肿瘤(癌症)患者之家