Scientists are zeroing in on a protein called BRD4, which plays a role in fueling tumor growth, especially in its most stubborn form, castration-resistant prostate cancer (CRPC). A new drug, MT-4561, is being tested in a clinical trial that could offer a lifeline by attacking BRD4.

BRD4, a member of the BET protein family, acts like a master switch, turning on genes that help cancer cells multiply and spread. Research shows it’s a key culprit in CRPC, where it ramps up genes like c-Myc and Bcl-2 to keep tumors thriving. It also fuels metastasis by tweaking proteins like Snail and Slug, enabling cancer cells to break free and invade other tissues. Beyond that, BRD4 teams up with HOXB13, a protein tied to aggressive cancer, and boosts KDM5C, which shuts down PTEN, a gene that normally keeps tumors in check. This cascade, dubbed the BRD4-KDM5C-PTEN axis, is a major driver of CRPC’s evolution.
Studies, including some published in Molecular Cancerand Nature, reveal BRD4 is overactive in advanced prostate cancer, spelling worse odds for patients.

Lab tests show that blocking BRD4 triggers cancer cell death and slows growth by boosting protective genes like FOXO1 while curbing harmful ones like c-Myc. BRD4 also meddles in DNA repair and gene rearrangements common in prostate cancer, making it an even better target for new drugs.

Unlike older drugs that merely block BRD4, MT-4561 destroys it through a process called ubiquitin-proteasomal degradation. The Phase I/II trial (NCT06943521) is testing MT-4561 in patients with advanced solid tumors, including prostate cancer, also its neuroendocrine variant.

Clinical trial.