Mocetinostat (MGCD0103): A Comprehensive Monograph on a Spectrum-Selective HDAC Inhibitor in Oncology

Section 1: Introduction and Overview

Introduction to Epigenetic Therapy in Oncology

The field of oncology has progressively evolved beyond cytotoxic and targeted therapies to embrace strategies that manipulate the fundamental regulatory machinery of the cancer cell. Among the most promising of these are epigenetic therapies, which target the mechanisms that control gene expression without altering the underlying DNA sequence.[1] A central process in this regulatory network is the dynamic acetylation and deacetylation of histone proteins. Histone acetyltransferases (HATs) add acetyl groups to lysine residues on histone tails, creating a relaxed chromatin structure that permits gene transcription. Conversely, histone deacetylases (HDACs) remove these acetyl groups, leading to chromatin condensation and transcriptional repression.[2]

In carcinogenesis, the dysregulation of HDACs is a common event. The overexpression or aberrant activity of these enzymes can lead to the inappropriate silencing of critical tumor suppressor genes, which are the body's natural defense against cancer.[5] This epigenetic silencing contributes to uncontrolled cell proliferation, survival, and differentiation, making HDACs a validated and compelling therapeutic target. The development of HDAC inhibitors (HDACis) represents a rational approach to reverse this pathological gene silencing, restore normal cellular function, and thereby inhibit tumor growth.[1]

Positioning Mocetinostat within the HDAC Inhibitor Landscape