Episensitization: Therapeutic Tumor Resensitization by Epigenetic Agents: A Review and Reassessment

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 14, 10 Issues, 2014


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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  • 85th of 202 in Oncology

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Episensitization: Therapeutic Tumor Resensitization by Epigenetic Agents: A Review and Reassessment

Author(s): Oronsky Bryan, Oronsky Neil, Knox Susan, Fanger Gary and Scicinski Jan

Affiliation: RadioRx, Inc 800 W El Camino Real, Suite 180, Mountain View CA 94040.

Abstract

Resistance to chemotherapy, biological and targeted therapies is an important clinical problem. Resistance can arise and/or be selected for via multiple mechanisms of action. Unfortunately, acquired resistance to antitumor agents or regimens is nearly inevitable in all patients with metastatic disease. Until recently, it was believed that this resistance was unalterable and irreversible, rendering retreatment with the same or similar drugs futile in most cases. However, the introduction of epigenetic therapies, including HDAC inhibitors and DNA methyltransferase inhibitors (DNMTIs), provide oncologists with new strategies to potentially overcome this resistance. For example, if chemoresistance is the product of multiple non-genetic alterations, which develop and accumulate over time in response to treatment, then the ability to epigenetically modify the tumor to reconfigure it back to its baseline non-resistant state, holds tremendous promise for the treatment of advanced, metastatic cancer. This minireview aims (1) to explore the potential mechanisms by which a group of small molecule agents including HDACs (entinostat and vorinostat), DNA hypomethylating agents such as the DNMTIs (decitabine (DEC), 5-azacytidine (5-AZA)) and redox modulators (RRx-001) may reprogram the tumors from a refractory to non-refractory state, (2) highlight some recent findings in this area, and (3) discuss the therapeutic potential of resensitization approaches with formerly failed chemotherapies

Keywords: Epigenetics, HDAC inhibitors, reactive oxygen species, resensitization

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Article Details

Volume: 14
First Page: 1
Last Page: 7
Page Count: 7
DOI: 10.2174/1871520614666140418144610
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