Epigenetic dynamics in cancer stem cell dormancy
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Epigenetic dynamics in cancer stem cell dormancy Alejandra I. Ferrer 1 & Jonathan R. Trinidad 2 & Oleta Sandiford 1 & Jean-Pierre Etchegaray 2 & Pranela Rameshwar 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Cancer remains one of the most challenging diseases despite significant advances of early diagnosis and therapeutic treatments. Cancerous tumors are composed of various cell types including cancer stem cells capable of self-renewal, proliferation, differentiation, and invasion of distal tumor sites. Most notably, these cells can enter a dormant cellular state that is resistant to conventional therapies. Thereby, cancer stem cells have the intrinsic potential for tumor initiation, tumor growth, metastasis, and tumor relapse after therapy. Both genetic and epigenetic alterations are attributed to the formation of multiple tumor types. This review is focused on how epigenetic dynamics involving DNA methylation and DNA oxidations are implicated in breast cancer and glioblastoma multiforme. The emergence and progression of these cancer types rely on cancer stem cells with the capacity to enter quiescence also known as a dormant cellular state, which dictates the distinct tumorigenic aggressiveness between breast cancer and glioblastomas. Keywords Cancer stem cells . Epigenetics . TET . Glioblastoma multiforme . Breast cancer . Dormancy . Bone marrow
1 Introduction Epigenetic dynamics are essential for normal tissue homeostasis, and their disruption may lead to changes in gene expression networks associated with various types of cancer. This review focuses on epigenetic alterations associated with breast cancer (BC) and glioblastoma multiforme (GBM). BC is the most frequent cancer type among women and remains the leading cause of cancer-related death worldwide. This is in line with an increased trend for BC over the last decade, especially in younger women. In the USA, BC represents over one-fifth of all cancers, with over 268,000 new cases in 2019, according to the national cancer institute [1]. GBM is the sixteenth most common cancer with over 23,000 new cases in 2019, accounting of approximately ~ 50% of primary brain
Alejandra I. Ferrer and Jonathan R. Trinidad contributed equally to this work. * Jean-Pierre Etchegaray [email protected] * Pranela Rameshwar [email protected] 1
Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
2
Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA
tumors and poor survival rate of 6 to 12 months [2, 3]. Here, we discuss the current literature on BC and GBM with emphasis on the epigenetic changes related to DNA methylation and DNA oxidations that could act as roadblocks for cancer treatments [1–6]. We will discuss how these epigenetic dynamics facilitating tumorigenesis could be interrogated to develop new treatment strategies. A major issue for cancer relapse is the ability of the tumor cells to survive during dormancy state. Tumor dormancy can exist for decades in a p
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