OCRA-Funded Research Uncovers New Checkpoint Mechanism, Potential New Therapeutic Target

New research from The Wistar Institute and Peter MacCallum Cancer Center has uncovered a previously unknown checkpoint mechanism for gene expression, that may open up new avenues for transcription-based targeted cancer therapies in the future.

This exciting study, published in the cancer journal Cell, was made possible in part by an OCRA research grant to Dr. Rugang Zhang at The Wistar Institute.

Gene expression determines how well cells can perform their functions, adapt to their environments, and respond to external stimuli, and is a crucial concept in understanding how cancer cells can develop and spread.

Says study co-author Allesandro Gardini, PhD, in Cell, “Cancer is a consequence of altered gene expression, as turning on or off one or more genes at the wrong time or in the wrong cells can dramatically alter their overall behavior and lead to unrestrained growth.”

In this study, researchers investigated the protein phosphatase 2A (PP2A)-Integrator-CDK9 Axis, a specific checkpoint mechanism for gene expression that is in charge of regulating the activity of the RNA polymerase II enzyme (RNAPII). Disruption of this mechanism leads to unrestricted gene transcription and is implicated in cancer.

Researchers found that a combination of CDK9 inhibition and PP2A activation were shown to enhance anti-cancer effects in preclinical models of both solid tumors and blood cancers, paving the way for potential new avenues of transcription-based anticancer therapy.

Read more about the study, “The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer,” in Cell.