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

Abstract:

:Resistance to chemotherapy, biological and targeted therapies is an important clinical problem. Resistance can arise and/or be selected for 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), has provided 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.

authors

Oronsky B,Oronsky N,Knox S,Fanger G,Scicinski J

doi

10.2174/1871520614666140418144610

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

1121-7

issue

8

eissn

1871-5206

issn

1875-5992

pii

ACAMC-EPUB-60178

journal_volume

14

pub_type

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