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Epigenetic Targeting of Platinum Resistant Testicular Cancer

Daniel Sonnenburg, Michael J Spinella, Costantine Albany1

  • 1Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, 535 Barnhull Drive RT-473, Indianapolis, IN 46202, USA. calbany@iu.edu.

Current Cancer Drug Targets
|December 24, 2015
PubMed

Insights

Epigenetic aberrations, particularly DNA hypermethylation, contribute to chemotherapy resistance in testicular cancer. Demethylating agents show promise in overcoming platinum resistance in refractory germ cell tumors.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Epigenetic aberrations are implicated in tumor development and progression.
  • Little is known about epigenetic alterations in testicular cancer, especially platinum-refractory germ cell tumors.
  • Testicular cancers exhibit unique epigenetic profiles, including extensive DNA hypomethylation.

Purpose of the Study:

  • To review the role of epigenetic aberrations in testicular cancer, focusing on chemotherapy resistance.
  • To explore the potential of DNA methylation inhibitors in treating refractory testicular germ cell tumors.

Main Methods:

  • Review of emerging data from clinical specimens and preclinical studies.
  • Analysis of epigenetic profiles in germ cell derived testicular cancers.
  • Evaluation of testicular cancer cell sensitivity to demethylating agents.

Main Results:

  • DNA hypermethylation is linked to chemotherapy resistance and poor outcomes in testicular germ cell tumors.
  • Platinum-refractory testicular cancer cells demonstrate sensitivity to low-dose demethylating agents.
  • Preclinical studies suggest potential for epigenetic drugs in overcoming acquired drug resistance.

Conclusions:

  • DNA methylation inhibitors combined with chemotherapy may overcome acquired drug resistance in testicular cancer.
  • Epigenetic therapy holds promise for treating refractory testicular germ cell tumors.
  • Further clinical investigation of DNA methylation inhibitors is warranted for refractory testicular cancer.

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