Intratumoral heterogeneity can occur via phenotype transitions, often after chronic exposure to targeted anticancer agents. This process, termed lineage plasticity, is associated with acquired independence to an initial oncogenic driver, resulting in treatment failure. In non-small cell lung cancer (NSCLC) and prostate cancers, lineage plasticity manifests when the adenocarcinoma phenotype transforms into neuroendocrine (NE) disease. The exact molecular mechanisms involved in this NE transdifferentiation remain elusive. In small cell lung cancer (SCLC), plasticity from NE to nonNE phenotypes is driven by NOTCH signaling. Herein we review current understanding of NE lineage plasticity dynamics, exemplified by prostate cancer, NSCLC, and SCLC.

肿瘤内异质性可以通过表型转变而发生，通常是在长期暴露于靶向抗癌药物之后。这个过程被称为谱系可塑性，与获得的对最初致癌驱动因素的独立性有关，从而导致治疗失败。在非小细胞肺癌（NSCLC）和前列腺癌中，当腺癌表型转变为神经内分泌（NE）疾病时，谱系可塑性就会显现出来。这种 NE 转分化所涉及的确切分子机制仍然难以捉摸。在小细胞肺癌 (SCLC) 中，从 NE 到非 NE 表型的可塑性是由 NOTCH 信号传导驱动的。在此，我们回顾了目前对 NE 谱系可塑性动态的理解，以前列腺癌、NSCLC 和 SCLC 为例。