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Updated: Apr 28, 2026

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Episensitization: therapeutic tumor resensitization by epigenetic agents: a review and reassessment

Bryan Oronsky, Neil Oronsky, Susan Knox

  • 1RadioRx, Inc, 800 W El Camino Real, Suite 180, Mountain View CA 94040. jscicinski@radiorx.com.

Anti-Cancer Agents in Medicinal Chemistry
|June 5, 2014
PubMed

Insights

Epigenetic therapies like HDAC inhibitors and DNMTIs can potentially reverse chemotherapy resistance in metastatic cancer. These agents may reprogram tumors, offering new hope for resensitizing patients to previously ineffective treatments.

Area of Science:

  • Oncology
  • Epigenetics
  • Pharmacology

Background:

  • Acquired resistance to chemotherapy, biological, and targeted therapies is a significant clinical challenge in metastatic cancer.
  • This resistance was historically considered irreversible, limiting retreatment options.
  • Epigenetic therapies offer novel strategies to potentially overcome established drug resistance.

Purpose of the Study:

  • To explore mechanisms of small molecule agents in reprogramming tumors from a resistant to a non-resistant state.
  • To highlight recent findings on epigenetic reprogramming for overcoming cancer resistance.
  • To discuss the therapeutic potential of resensitization strategies with previously failed chemotherapies.

Main Methods:

  • Review of literature on epigenetic modifiers including HDAC inhibitors (entinostat, vorinostat) and DNA methyltransferase inhibitors (DNMTIs) like decitabine (DEC) and 5-azacytidine (5-AZA).
  • Exploration of redox modulators (RRx-001) in tumor reprogramming.
  • Analysis of recent findings and therapeutic potential for resensitization approaches.

Main Results:

  • Epigenetic agents may reverse non-genetic alterations contributing to chemoresistance.
  • Small molecules can potentially reconfigure tumors to a non-resistant state.
  • Resensitization approaches show promise for treating advanced metastatic cancer.

Conclusions:

  • Epigenetic therapies hold significant promise for overcoming acquired resistance in metastatic cancer.
  • Reprogramming tumors using agents like HDAC inhibitors, DNMTIs, and redox modulators can restore sensitivity to chemotherapy.
  • This approach offers a potential strategy for retreatment in patients with advanced disease.

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