Targeting Cancer Cell Dormancy

Trends Pharmacol Sci. 2019 Feb;40(2):128-141. doi: 10.1016/j.tips.2018.12.004. Epub 2019 Jan 3.

Abstract

Cancer cell dormancy is a process whereby cells enter reversible cell cycle arrest, termed quiescence. Quiescence is essential for cancer cells to acquire additional mutations, to survive in a new environment and initiate metastasis, to become resistant to cancer therapy, and to evade immune destruction. Thus, dormant cancer cells are considered to be responsible for cancer progression. As we start to understand the mechanisms that enable quiescence, we can begin to develop pharmacological strategies to target dormant cancer cells. Herein, we summarize the major molecular mechanisms underlying the dormancy of disseminated tumor cells and drug-tolerant persister cells. We then analyze the current pharmacological strategies aimed (i) to keep cancer cells in the harmless dormant state, (ii) to reactivate dormant cells to increase their susceptibility to anti-proliferative drugs, and (iii) to eradicate dormant cancer cells.

Keywords: cancer dormancy; disseminated tumor cells; drug-tolerant persister cells; epigenetic inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle Checkpoints / drug effects
  • Cell Transformation, Neoplastic
  • Drug Resistance, Neoplasm
  • Humans
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasms / drug therapy
  • Neoplasms / pathology*
  • Tumor Escape

Substances

  • Antineoplastic Agents