Stemness regulation in prostate cancer: prostate cancer stem cells and targeted therapy

Ann Med. 2025 Dec;57(1):2442067. doi: 10.1080/07853890.2024.2442067. Epub 2024 Dec 23.

Abstract

Background: Increasing evidence indicates that cancer stem cells (CSCs) and cancer stem-like cells form a special subpopulation of cells that are ubiquitous in tumors. These cells exhibit similar characteristics to those of normal stem cells in tissues; moreover, they are capable of self-renewal and differentiation, as well as high tumorigenicity and drug resistance. In prostate cancer (PCa), it is difficult to kill these cells using androgen signaling inhibitors and chemotherapy drugs. Consequently, the residual prostate cancer stem cells (PCSCs) mediate tumor recurrence and progression.

Objective: This review aims to provide a comprehensive and up-to-date overview of PCSCs, with a particular emphasis on potential therapeutic strategies targeting these cells.

Methods: After searching in PubMed and Embase databases using 'prostate cancer' and 'cancer stem cells' as keywords, studies related were compiled and examined.

Results: In this review, we detail the origin and characteristics of PCSCs, introduce the regulatory pathways closely related to CSC survival and stemness maintenance, and discuss the link between epithelial-mesenchymal transition, tumor microenvironment and tumor stemness. Furthermore, we introduce the currently available therapeutic strategies targeting CSCs, including signaling pathway inhibitors, anti-apoptotic protein inhibitors, microRNAs, nanomedicine, and immunotherapy. Lastly, we summarize the limitations of current CSC research and mention future research directions.

Conclusion: A deeper understanding of the regulatory network and molecular markers of PCSCs could facilitate the development of novel therapeutic strategies targeting these cells. Previous preclinical studies have demonstrated the potential of this treatment approach. In the future, this may offer alternative treatment options for PCa patients.

Keywords: Prostate cancer; cancer stem cells; cancer stem-like cell; stemness; targeted therapy; tumor heterogeneity.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Immunotherapy / methods
  • Male
  • MicroRNAs / metabolism
  • Molecular Targeted Therapy / methods
  • Neoplastic Stem Cells* / drug effects
  • Neoplastic Stem Cells* / metabolism
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / therapy
  • Signal Transduction / drug effects
  • Tumor Microenvironment*

Substances

  • MicroRNAs
  • Antineoplastic Agents