Samriddhi Shukla1, Syed Musthapa Meeran2. 1. Laboratory of Cancer Epigenetics, Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India. 2. Laboratory of Cancer Epigenetics, Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India. Electronic address: s.musthapa@cdri.res.in.
Abstract
BACKGROUND: Epigenetic alterations including DNA methylation and histone modifications are the key factors in the differentiation of stem cells into different tissue subtypes. The generation of cancer stem cells (CSCs) in the process of carcinogenesis may also involve similar kind of epigenetic reprogramming where, in contrast, it leads to the loss of expression of genes specific to the differentiated state and regaining of stem cell-specific characteristics. The most important predicament with treatment of cancers includes the non-responsive quiescent CSC. SCOPE OF REVIEW: The distinctive capabilities of the CSCs make cancer treatment even more difficult as this population of cells tends to remain quiescent for longer intervals and then gets reactivated leading to tumor relapse. Therefore, the current review is aimed to focus on recent advances in understanding the relation of epigenetic reprogramming to the generation, self-renewal and proliferation of CSCs. MAJOR CONCLUSION: CSC-targeted therapeutic approaches would improve the chances of patient survival by reducing the frequency of tumor relapse. Differentiation therapy is an emerging therapeutic approach in which the CSCs are induced to differentiate from their quiescent state to a mature differentiated form, through activation of differentiation-related signalling pathways, miRNA-mediated alteration and epigenetic differentiation therapy. Thus, understanding the origin of CSC and their epigenetic regulation is crucial to develop treatment strategy against not only for the heterogeneous population of cancer cells but also to CSCs. GENERAL SIGNIFICANCE: Characterizing the epigenetic marks of CSCs and the associated signalling cascades might help in developing therapeutic strategies against chemo-resistant cancers.
BACKGROUND: Epigenetic alterations including DNA methylation and histone modifications are the key factors in the differentiation of stem cells into different tissue subtypes. The generation of cancer stem cells (CSCs) in the process of carcinogenesis may also involve similar kind of epigenetic reprogramming where, in contrast, it leads to the loss of expression of genes specific to the differentiated state and regaining of stem cell-specific characteristics. The most important predicament with treatment of cancers includes the non-responsive quiescent CSC. SCOPE OF REVIEW: The distinctive capabilities of the CSCs make cancer treatment even more difficult as this population of cells tends to remain quiescent for longer intervals and then gets reactivated leading to tumor relapse. Therefore, the current review is aimed to focus on recent advances in understanding the relation of epigenetic reprogramming to the generation, self-renewal and proliferation of CSCs. MAJOR CONCLUSION: CSC-targeted therapeutic approaches would improve the chances of patient survival by reducing the frequency of tumor relapse. Differentiation therapy is an emerging therapeutic approach in which the CSCs are induced to differentiate from their quiescent state to a mature differentiated form, through activation of differentiation-related signalling pathways, miRNA-mediated alteration and epigenetic differentiation therapy. Thus, understanding the origin of CSC and their epigenetic regulation is crucial to develop treatment strategy against not only for the heterogeneous population of cancer cells but also to CSCs. GENERAL SIGNIFICANCE: Characterizing the epigenetic marks of CSCs and the associated signalling cascades might help in developing therapeutic strategies against chemo-resistant cancers.
Authors: Bárbara Kunzler Souza; Patrícia Luciana da Costa Lopez; Pâmela Rossi Menegotto; Igor Araujo Vieira; Nathalia Kersting; Ana Lúcia Abujamra; André T Brunetto; Algemir L Brunetto; Lauro Gregianin; Caroline Brunetto de Farias; Carol J Thiele; Rafael Roesler Journal: Mol Neurobiol Date: 2018-02-03 Impact factor: 5.590