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Biochem Pharmacol. 2019 Apr;162:169-176. doi: 10.1016/j.bcp.2018.11.004. Epub 2018 Nov 9.

Dormant, quiescent, tolerant and persister cells: Four synonyms for the same target in cancer.

Author information

1
INSERM, U1232, Institut de Cancérologie de l'Ouest, Tea 9 "Apopotosis and Tumor Progression", LabCT, CRCINA, Université de Nantes, Université d'Angers, 44805 cedex, Saint Herblain, France. Electronic address: francois.vallette@univ-nantes.fr.
2
INSERM, U1232, Institut de Cancérologie de l'Ouest, Tea 9 "Apopotosis and Tumor Progression", LabCT, CRCINA, Université de Nantes, Université d'Angers, 44805 cedex, Saint Herblain, France; Service de Toxicology, Faculty of Pharmacy, Nantes, France.
3
INSERM, UMR1238, Université de Nantes, Faculty of Medicine, rue Gaston Veil, Nantes, France.
4
INSERM, U1232, Institut de Cancérologie de l'Ouest, Tea 9 "Apopotosis and Tumor Progression", LabCT, CRCINA, Université de Nantes, Université d'Angers, 44805 cedex, Saint Herblain, France.
5
INSERM, U1232, Institut de Cancérologie de l'Ouest, Tea 9 "Apopotosis and Tumor Progression", LabCT, CRCINA, Université de Nantes, Université d'Angers, 44805 cedex, Saint Herblain, France; INSERM, European Associated Laboratory "Sarcoma Research Unit", Department of Oncology and Metabolism, Medical School, University of Sheffield, United Kingdom. Electronic address: dominique.heymann@univ-nantes.fr.

Abstract

Although many drugs/treatments are now available for most diseases, too often, resistance to these treatments impedes complete therapeutic success. Acquired resistance is a major problem in many pathologies but it is an acute one in cancers and infections. This is probably because these diseases often require long durations of treatment, which ascribe to the selection of resistant cells. However, the actual mechanisms implicated in the selection process are still under debate. It is becoming increasingly clear that resistance is associated with the heterogeneity of cancer cells or micro-organisms and that multiple mechanisms underlie the emergence of drug-resistant subpopulations. Recently, it has been suggested that a subpopulation of drug tolerant cells present in cancer populations and called "persisters" play a major role in this resistance. Recent studies have shown that microorganisms share similar properties. Still, how persister/tolerant cells intervene in the development of resistance is not completely elucidated but seems to be related to epigenetic changes in treated cells and the capacity of persisters to modulate and/or highjack their microenvironment. Due to the complexity of this process, the input from mathematicians, as well as new methods of bioinformatics and statistics, is necessary to fully comprehend the acquisition of resistance/tolerance deriving from and leading to the heterogeneous cell populations. The present review will give a brief overview of the most recent data available on drug tolerant cells in cancers and their similarities with microorganisms.

KEYWORDS:

Cell dormancy; Drug resistance; Drug tolerance; Persisters; Quiescence; Recurrent disease

PMID:
30414937
DOI:
10.1016/j.bcp.2018.11.004
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