Theranostics 2020; 10(14):6261-6277. doi:10.7150/thno.42523

Review

Epigenetics and metabolism at the crossroads of stress-induced plasticity, stemness and therapeutic resistance in cancer

Dinoop Ravindran Menon1*, Heinz Hammerlindl2*, Joachim Torrano2, Helmut Schaider2✉, Mayumi Fujita1,3,4✉

1. Department of Dermatology, University of Colorado School of Medicine, Aurora, CO, USA
2. The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, OLD, Australia
3. Eastern Colorado VA Health Care System, Aurora CO, USA
4. Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA
*These authors contributed equally to the study

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Citation:
Ravindran Menon D, Hammerlindl H, Torrano J, Schaider H, Fujita M. Epigenetics and metabolism at the crossroads of stress-induced plasticity, stemness and therapeutic resistance in cancer. Theranostics 2020; 10(14):6261-6277. doi:10.7150/thno.42523. Available from https://www.thno.org/v10p6261.htm

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Abstract

Despite the recent advances in the treatment of cancers, acquired drug resistance remains a major challenge in cancer management. While earlier studies suggest Darwinian factors driving acquired drug resistance, recent studies point to a more dynamic process involving phenotypic plasticity and tumor heterogeneity in the evolution of acquired drug resistance. Chronic stress after drug treatment induces intrinsic cellular reprogramming and cancer stemness through a slow-cycling persister state, which subsequently drives cancer progression. Both epigenetic and metabolic mechanisms play an important role in this dynamic process. In this review, we discuss how epigenetic and metabolic reprogramming leads to stress-induced phenotypic plasticity and acquired drug resistance, and how the two reprogramming mechanisms crosstalk with each other.

Keywords: Epigenetics, metabolism, stress-induced plasticity, stemness