Title:Rational Design and Development of HDAC Inhibitors for Breast Cancer Treatment
Volume: 27
Issue: 45
Author(s): Deepansh Mody, Julie Bouckaert, Savvas N. Savvides and Vibha Gupta*
Affiliation:
- Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, Noida, UP, 201307,India
Keywords:
Histone deacetylases, HDACi, rational drug discovery, structural insights, breast cancer, differential HDAC expression, HDACisoform
selectivity.
Abstract:
Background: Breast cancer is the most prevalent cancer amongst females across the globe, and with
over 2 million new cases reported in 2018, it poses a huge economic burden to the already dwindling public
health. A dearth of therapies in the pipeline to treat triple-negative breast cancers and acquisition of resistance
against the existing line of treatments urge the need to strategize novel therapeutics in order to add new drugs to
the pipeline. HDAC inhibitors (HDACi) is one such class of small molecule inhibitors that target histone
deacetylases to bring about chromosomal remodelling and normalize dysregulated gene expression that marks
breast cancer progression.
Objective: While four HDACi have been approved by the FDA for the treatment of different cancer types, no
HDACi is specifically earmarked for clinical management of breast cancer. Owing to the differential HDAC
expression pertaining to different types of breast cancers, isoform-selective HDAC inhibitors need to be discovered.
Conclusion: This review attempts to set the stage for the rational structure-based discovery of isoform-selective
HDACi by providing structural insights into different HDACs and their catalytic folds based on their classes
and individual landscape. The development of inhibitors in accordance with the differential expression of
HDAC isoforms exhibited in breast cancer cells is a promising strategy to rationally design selective and effective
inhibitors, adopting a ‘personalized-medicine’ approach.
