The epigenetics of ovarian cancer drug resistance and resensitization

Curtis Balch, Tim H.M. Huang, Robert Brown, Kenneth P. Nephew

Research output: Contribution to journalReview articlepeer-review

131 Scopus citations

Abstract

Ovarian cancer is the most lethal of all gynecologic neoplasms. Early-stage malignancy is frequently asymptomatic and difficult to detect and thus, by the time of diagnosis, most women have advanced disease. Most of these patients, although initially responsive, eventually develop and succumb to drug-resistant metastases. The success of typical postsurgical regimens, usually a platinum/taxane combination, is limited by primary tumors being intrinsically refractory to treatment and initially responsive tumors becoming refractory to treatment, due to the emergence of drug-resistant tumor cells. This review highlights a prominent role for epigenetics, particularly aberrant DNA methylation and histone acetylation, in both intrinsic and acquired drug-resistance genetic pathways in ovarian cancer. Administration of therapies that reverse epigenetic "silencing" of tumor suppressors and other genes involved in drug response cascades could prove useful in the management of drug-resistant ovarian cancer patients. In this review, we summarize recent advances in the use of methyltransferase and histone deacetylase inhibitors and possible synergistic combinations of these to achieve maximal tumor suppressor gene re-expression. Moreover, when used in combination with conventional chemotherapeutic agents, epigenetic-based therapies may provide a means to resensitize ovarian tumors to the proven cytotoxic activities of conventional chemotherapeutics.

Original languageEnglish (US)
Pages (from-to)1552-1572
Number of pages21
JournalAmerican Journal of Obstetrics and Gynecology
Volume191
Issue number5
DOIs
StatePublished - Nov 1 2004

Keywords

  • Chemosensitization
  • DNA methylation
  • Drug resistance
  • Epigenetics
  • Histone deacetylase inhibitor
  • Ovarian cancer

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

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