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Epigenetic treatment combinations to effectively target cisplatin-resistant germ cell tumors: past, present, and

C Oing1,2, M A Skowron3, C Bokemeyer1

  • 1Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Andrology
|March 30, 2019
PubMed
Abstract

Insights

Epigenetic therapies targeting DNA methylation and histone acetylation show promise in overcoming chemotherapy resistance in germ cell tumors. Further research is needed to define optimal drug combinations for improved patient outcomes.

Area of Science:

  • Oncology
  • Epigenetics
  • Cancer Therapeutics

Background:

  • Type II germ cell tumors are the most common malignancy in men aged 15-45.
  • While cure rates exceed 90%, 10-15% of advanced cases exhibit treatment resistance.
  • Refractory germ cell tumors require novel therapeutic strategies.

Purpose of the Study:

  • To review epigenetic mechanisms driving resistance to standard chemotherapy in germ cell tumors.
  • To identify promising epigenetic targets for novel treatment approaches.

Main Methods:

  • Comprehensive literature search of PubMed and MEDLINE databases.
  • Inclusion of original and review articles on germ cell tumor resistance and epigenetic treatment.
  • Hand-searching of review articles for additional relevant studies.

Main Results:

  • DNA hypermethylation, histone acetylation, and bromodomain proteins are key epigenetic targets.
  • Inhibitors of DNA methyltransferases, histone deacetylases, and bromodomain proteins show efficacy.
  • Epigenetic drugs induce differentiation, reduce pluripotency, and re-sensitize cells to cisplatin.

Conclusions:

  • Epigenetic treatments offer potential to reduce treatment burden and overcome cisplatin resistance.
  • Combined epigenetic approaches may enhance therapeutic activity.
  • Further pre-clinical and clinical research is crucial to optimize epigenetic treatments for germ cell tumors.
Keywords:
DNMT inhibitionHDAC inhibitioncisplatin resistancecombination therapyepigeneticsgerm cell tumours

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