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Ponnusamy et al. Cancer Drug Resist 2019;2:297-312 Cancer
DOI: 10.20517/cdr.2018.11 Drug Resistance

Review Open Access

Role of cellular reprogramming and epigenetic
dysregulation in acquired chemoresistance in breast

cancer

Logeswari Ponnusamy , Prathap Kumar S. Mahalingaiah , Yu-Wei Chang , Kamaleshwar P. Singh 1
1
1,2
1,3
1 Department of Environmental Toxicology, The Institute of Environmental and Human Health (TIEHH), Texas Tech University,
Lubbock, Texas 79409, USA.
2 Metabolism and Safety, Zoetis, Kalamazoo, Michigan 49007, USA [current affiliation].
3 Preclinical Safety, AbbVie, North Chicago, Illinois 60085, USA [current affiliation].
Correspondence to: Dr. Kamaleshwar P. Singh, Department of Environmental Toxicology, The Institute of Environmental and
Human Health (TIEHH), Texas Tech University, Lubbock, Texas 79409, USA. E-mail: kamaleshwar.singh@ttu.edu
How to cite this article: Ponnusamy L, Mahalingaiah PKS, Chang YW, Singh KP. Role of cellular reprogramming and epigenetic
dysregulation in acquired chemoresistance in breast cancer. Cancer Drug Resist 2019;2:297-312.
http://dx.doi.org/10.20517/cdr.2018.11
Received: 19 Dec 2018 First Decision: 12 Feb 2019 Revised: 23 Feb 2019 Accepted: 25 Mar 2019 Published: 19 Jun 2019

Science Editor: Aamir Ahmad Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Acquired resistance to chemotherapy is a major limitation in clinical treatment for breast cancer. Accumulating evidence
from in vitro, in vivo and clinical studies suggest that acquired chemoresistance is progressive, multifactorial and
involve genetic and epigenetic aberrations. Among various mechanisms that contribute to chemoresistance, cellular
reprogramming has extensively been implicated in breast cancer resistance lately. Cellular reprogramming events such
as acquisition of epithelial to mesenchymal transition (EMT) and cancer stemness (CSCs) not only provide cancer
cells with reversible phenotypic plasticity and survival advantage against cytotoxicity but also leads to aggressiveness,
metastasis, clinical resistance, tumor recurrence and poor survival. The transient and reversible nature of cellular
reprogramming processes and their controlled interaction with epigenetic regulatory complexes strongly support the
involvement of dynamic epigenetic regulatory network in governing the cellular reprogramming and associated acquired
chemoresistance. Further, epigenetic modulations are also gaining interest as promising interventions addressing the
cancer cell reprogramming machinery to overcome acquired chemoresistance. This review discusses the previous
reports and our recent findings that lead to current understanding of epigenetic dysregulation dictating the cellular
reprogramming processes such as acquisition of EMT and CSCs phenotype and how they co-ordinate to establish
acquired drug resistance in breast cancer.

Keywords: Chemoresistance, cellular reprogramming, DNA methylation, histone modifications, breast cancer, epithelial
to mesenchymal transition, cancer stem cell
© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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