PDF(Pubmed)
Abstract：
Lung cancer is the leading cause of cancer death and includes two major types: non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), accounting for 85% and 15% of cases, respectively. Non-small-cell lung cancer harboring actionable driver mutations is generally treated with tyrosine kinase inhibitors (TKIs) molecularly targeting individual oncogenes. Although TKIs have greatly contributed to better clinical outcomes, acquired resistance to them inevitably occurs. Histologic or lineage transformation is a rare but well-documented off-target mechanism associated with acquired resistance, and has been identified in settings following treatment with multiple different TKIs and other drugs. It includes neuroendocrine transformation, squamous cell transformation, and epithelial-to-mesenchymal transition. Here, we review the clinicopathologic features of transformed tumors and current understanding of the key genetic alterations and biologic mechanism of lineage transformation in NSCLC, particularly TKI-triggered transformation.
摘要：
肺癌是癌症死亡的主要原因，包括两种主要类型：非小细胞肺癌（NSCLC）和小细胞肺癌（SCLC）。占病例的85%和15%，分别。通常用分子靶向单个癌基因的酪氨酸激酶抑制剂（TKIs）治疗具有可操作驱动突变的非小细胞肺癌。尽管TKIs极大地促进了更好的临床结果，对它们的抵抗不可避免地发生。组织学或谱系转化是一种罕见但有据可查的与获得性抗性相关的脱靶机制。并且在使用多种不同TKIs和其他药物治疗后的环境中被鉴定。它包括神经内分泌转化，鳞状细胞转化，和上皮-间质转化。这里,我们回顾了转化肿瘤的临床病理特征，以及对NSCLC谱系转化的关键遗传改变和生物学机制的最新认识。特别是TKI触发的转换。
