Epigenetic alterations as therapeutic targets in Testicular Germ Cell Tumours : current and future application of 'epidrugs'

Epigenetics. 2021 Apr;16(4):353-372. doi: 10.1080/15592294.2020.1805682. Epub 2020 Aug 12.

Abstract

Testicular germ cell tumours (TGCTs) are heterogeneous neoplasms mostly affecting young-adult men. Despite high survival rates, some patients with disseminated disease acquire cisplatin resistance, entailing the need for less toxic therapies. Epigenetic alterations constitute an important feature of TGCTs, which are also implicated in resistance mechanism(s). These alterations might be used as potential targets to design epigenetic drugs. To date, several compounds have been explored and evaluated regarding therapeutic efficacy, making use of pre-clinical studies with in vitro and in vivo models, and some have already been explored in clinical trials. This review summarizes the several epigenetic mechanisms at play in these neoplasms, the current challenges in the field of TGCTs and critically reviews available data on 'epidrugs' in those tumours.

Keywords: Testicular germ cells tumours; epigenetics; histone modifications; methylation; microRNA; targeted therapies.

Publication types

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

MeSH terms

  • DNA Methylation
  • Epigenesis, Genetic
  • Humans
  • Male
  • Neoplasms, Germ Cell and Embryonal*
  • Testicular Neoplasms* / genetics

Supplementary concepts

  • Testicular Germ Cell Tumor

Grants and funding

The authors would like to acknowledge the support of the Programa Operacional Competitividade e Internacionalização (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the project EpiMarkGermCell (PTDC/MECONC/29043/2017). JL is recipient of a fellowship from FCT - Fundação para a Ciência e Tecnologia—(SFRH/BD/132751/2017). VM-G contract is funded by POCI-01-0145-FEDER-29043.