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

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.