Prostate cancer cell heterogeneity and plasticity: Insights from studies of genetically-engineered mouse models

Semin Cancer Biol. 2022 Jul:82:60-67. doi: 10.1016/j.semcancer.2021.06.016. Epub 2021 Jun 18.

Abstract

Although prostate adenocarcinoma lacks distinguishable histopathological subtypes, prostate cancer displays significant inter- and intratumor heterogeneity at the molecular level and with respect to disease prognosis and treatment response. In principle, understanding the basis for prostate cancer heterogeneity can help distinguish aggressive from indolent disease, and help overcome castration-resistance in advanced prostate cancer. In this review, we will discuss recent advances in understanding the cell types of origin, putative cancer stem cells, and tumor plasticity in prostate cancer, focusing on insights from studies of genetically engineered mouse models (GEMMs). We will also outline future directions for investigating tumor heterogeneity using mouse models of prostate cancer.

Keywords: Cancer stem cell; Castration-resistance; Cell of origin; Genetically engineered mouse model; Lineage plasticity; Tumor heterogeneity.

Publication types

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

MeSH terms

  • Animals
  • Disease Models, Animal
  • Humans
  • Male
  • Mice
  • Neoplastic Stem Cells / pathology
  • Prostate* / pathology
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / therapy