Hypothesizing that histone deacetylase inhibitors can be used to reverse multiple drug resistance

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Multidrug resistance (MDR) is a major challenge in cancer chemotherapy, primarily due to the overexpression of drug-efflux pumps like P-glycoprotein (P-gp).
• While P-gp is a known mediator of MDR, the mechanisms regulating its expression are not fully understood.
• Existing research on genetic polymorphism's role in P-gp expression has yielded conflicting results.

Purpose of the Study:

• To investigate the role of epigenetic variants in regulating multidrug resistance (MDR).
• To explore the potential of targeting epigenetic factors, specifically histone deacetylase inhibitors, as a strategy to overcome MDR.
• To elucidate the mechanism by which histone deacetylase inhibitors modulate P-gp expression.

Main Methods:

• Review of recent studies on MDR1 gene regulation, focusing on epigenetic modifications.
• Analysis of in vitro findings supporting the impact of epigenetic variance on MDR.
• Hypothesizing the mechanism of action for histone deacetylase inhibitors in modulating P-gp.

Main Results:

• Epigenetic variance is proposed to play a more significant role in MDR than genetic polymorphism.
• Adjusting epigenetic factors may alter MDR expression, potentially reversing multidrug resistance.
• Histone deacetylase inhibitors are identified as a potential therapeutic strategy to overcome MDR.

Conclusions:

• Epigenetic mechanisms are crucial in regulating multidrug resistance (MDR).
• Targeting epigenetic factors, particularly with histone deacetylase inhibitors, offers a promising approach to reverse MDR.
• Histone deacetylase inhibitors may exert a bidirectional modulatory effect on P-glycoprotein (P-gp), impacting MDR.