Epigenetic regulation of cancer dormancy as a plasticity mechanism for metastasis initiation

Maria Soledad Sosa, Emily Bernstein, Julio A. Aguirre-Ghiso

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Scopus citations

Abstract

Metastasis is responsible for the vast majority of cancer-related deaths. However, our understanding of this complex process is still vastly limited, as is the ability to prevent metastasis. Paradoxically, while clinical trials are commonly performed in patients with advanced metastatic disease, disseminated residual disease is rarely targeted. This eliminates a critical window of opportunity to prevent metastasis. Disseminated tumor cells (DTCs) that seed metastases can remain undetected years to decades after treatment of the primary tumor. Late relapse may be due to the ability of DTCs to survive in a quiescent or dormant state and evade therapies. Quiescence, a reversible growth arrest coupled to robust survival, has emerged as a fitting biological definition for dormancy of single DTCs, but these mechanisms remain as one of the least understood “black boxes” in cancer biology. Because of the reversible nature of dormancy, it has been proposed that epigenetic changes are key in regulating the onset, maintenance and reactivation from this state. This is mediated by the post-translational modification of histones (PTMs), ATP-dependent chromatin remodeling, DNA methylation, and the incorporation of specialized histone variants into chromatin. Many morphogenetic and micro-environmental cues like retinoic acid, TGFβs, hematopoietic stem cell dormancy regulating cues and BMPs are known to cause chromatin modifications that dictate cell fate; these same cues were linked to the induction of cancer cell dormancy. Despite progress in understanding cancer cell dormancy, key questions remain open regarding its epigenetic nature. In this chapter we attempt to address key questions related to this topic using available data or hypothetical scenarios to build a model to further dissect how cancer cell dormancy can be manipulated epigenetically as a therapeutic strategy.

Original languageEnglish (US)
Title of host publicationCancer Drug Discovery and Development
PublisherHumana Press Inc.
Pages1-16
Number of pages16
Edition9783319592404
DOIs
StatePublished - 2017
Externally publishedYes

Publication series

NameCancer Drug Discovery and Development
Number9783319592404
Volume0
ISSN (Print)2196-9906
ISSN (Electronic)2196-9914

Keywords

  • Chromatin
  • Dauer
  • Diapause
  • Differentiation
  • Dormancy
  • Drug resistance
  • Epigenome
  • Metastasis
  • Microenvironment
  • MRD
  • Niche
  • Relapse
  • Senescence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Drug Discovery

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