Lineage plasticity-mediated therapy resistance in prostate cancer

Asian J Androl. 2019 May-Jun;21(3):241-248. doi: 10.4103/aja.aja_41_18.

Abstract

Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.

Keywords: lineage plasticity; neuroendocrine; prostate cancer; therapy resistance; transdifferentiation.

Publication types

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

MeSH terms

  • Androgen Antagonists / therapeutic use
  • Androgen Receptor Antagonists / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Receptors, Androgen / drug effects

Substances

  • Androgen Antagonists
  • Androgen Receptor Antagonists
  • Receptors, Androgen