Application of iPS cell technology to cancer epigenome study: uncovering the mechanism of cell status conversion for drug resistance in tumor

Pathol Int. 2014 Jul;64(7):299-308. doi: 10.1111/pin.12180.

Abstract

Recent studies imply that cancer cells possess the ability to reversibly change their properties between a drug sensitive state and a drug resistant state accompanied by epigenetic changes. This evidence indicates that better understanding of cancer epigenetics is important for efficient cancer therapies. Nevertheless, it had been difficult to deeply examine the epigenetic mechanisms because of lack of the tools to actively modify coordinated epigenetic events. In this stagnant situation, the reprogramming technology established by Yamanaka and coworkers have shed a new light. The novel reprogramming technology has made it possible for researchers to artificially introduce epigenetic remodeling into somatic cells. Accordingly, we might be able to use this technology as a tool to introduce the coordinated epigenetic reorganization. In this review, we introduce the idea of cell state interconversion in cancer cells that is attributable to altered epigenetic regulations. We then depict the epigenetic modifications observed during the process of somatic cell reprogramming and give some examples of the difficulty in cancer cell reprogramming. Finally, we discuss how we can translate this reprogramming refractoriness of cancer cells into uncovering unique epigenetic regulations in cancer cells, which might be applicable eventually to the development of novel cancer therapeutics against drug resistant cancer cells.

Keywords: cancer cell reprogramming; cell status transition; drug resistant cancer cells; epigenetic flexibility; epigenetics; iPS cell technology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cellular Reprogramming / genetics
  • Cellular Reprogramming / physiology*
  • Drug Resistance, Neoplasm*
  • Epigenesis, Genetic*
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Neoplasms / genetics*
  • Neoplasms / therapy*