Cell-Intrinsic Mechanisms of Drug Tolerance to Systemic Therapies in Cancer

  • Leonce C
  • Saintigny P
  • Ortiz-Cuaran S
Citations of this article
Mendeley users who have this article in their library.
Get full text


In patients with cancer with metastatic disease, the rate of complete tumor response to systemic therapies is low, and residual lesions persist in the majority of patients due to early molecular adaptation in cancer cells. A growing body of evidence suggests that a subpopulation of drug-tolerant persister cells—a reversible phenotype characterized by reduced drug sensitivity and decreased cell proliferation—maintains residual disease and may serve as a reservoir for resistant phenotypes. The survival of these residual tumor cells can be caused by reactivation of specific signaling pathways, phenotypic plasticity (i.e., transdifferentiation), epigenetic or metabolic reprogramming, downregulation of apoptosis as well as transcriptional remodeling. In this review, we discuss the molecular mechanisms that enable adaptive survival in drug-tolerant cells. We describe the main characteristics and dynamic nature of this persistent state, and highlight the current therapeutic strategies that may be used to interfere with the establishment of drug-tolerant cells, as an alternative to improve objective response to systemic therapies and delay the emergence of resistance to improve long-term survival.




Leonce, C., Saintigny, P., & Ortiz-Cuaran, S. (2021). Cell-Intrinsic Mechanisms of Drug Tolerance to Systemic Therapies in Cancer. Molecular Cancer Research. https://doi.org/10.1158/1541-7786.mcr-21-0038

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free