Heterogeneity of cancer-associated fibroblasts: Opportunities for precision medicine

Cancer Sci. 2020 Aug;111(8):2708-2717. doi: 10.1111/cas.14537. Epub 2020 Jul 11.

Abstract

Despite marked development in cancer therapies during recent decades, the prognosis for advanced cancer remains poor. The conventional tumor-cell-centric view of cancer can only explain part of cancer progression, and thus a thorough understanding of the tumor microenvironment (TME) is crucial. Among cells within the TME, cancer-associated fibroblasts (CAFs) are attracting attention as a target for cancer therapy. However, CAFs present a heterogeneous population of cells and more detailed classification of CAFs and investigation of functions of each subset is needed to develop novel CAF-targeted therapies. In this context, application of newly developed approaches to single-cell analysis has already made an impact on our understanding of the heterogeneity of CAFs. Here, we review the recent literature on CAF heterogeneity and function, and discuss the possibility of novel therapies targeting CAF subsets.

Keywords: cancer progression; cancer-associated fibroblast; heterogeneity; single-cell RNA-sequencing; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cancer-Associated Fibroblasts / drug effects*
  • Cancer-Associated Fibroblasts / metabolism
  • Disease Progression
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genetic Heterogeneity
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Precision Medicine / methods*
  • RNA-Seq
  • Single-Cell Analysis
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics*

Substances

  • Antineoplastic Agents