Impact of Lineage Plasticity to and from a Neuroendocrine Phenotype on Progression and Response in Prostate and Lung Cancers

Mol Cell. 2020 Nov 19;80(4):562-577. doi: 10.1016/j.molcel.2020.10.033.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Lineage*
  • Cell Plasticity*
  • Disease Progression
  • Humans
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy
  • Male
  • Neuroendocrine Tumors / pathology*
  • Neuroendocrine Tumors / therapy
  • Phenotype*
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / therapy