Pharmacological Modulation of Transcriptional Coregulators in Cancer

Publication date: Available online 8 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Timothy R. Bishop, Yuxiang Zhang, Michael A. ErbUpon binding of transcription factors to cis-regulatory DNA sequences, transcriptional coregulators are required for the activation or suppression of chromatin-dependent transcriptional signaling. These coregulators are frequently implicated in oncogenesis via causal roles in dysregulated, malignant transcriptional control and represent one of the fastest-growing target classes in small-molecule drug discovery. However, challenges in targeting coregulators include identifying evidence of cancer-specific genetic dependency, matching the pharmacologically addressable protein fold to a functional role in disease pathology, and achieving the necessary selectivity to exploit a given genetic dependency. We discuss here how recent trends in cancer pharmacology have confronted these challenges, positioning coregulators as tractable targets in the development of new cancer therapies.
Source: Trends in Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research