Yale trial: experimental PROTAC drug bavdegalutamide lowers PSA in advanced prostate cancer

Researchers at Yale University in the United States reported encouraging results from a clinical trial of the experimental drug bavdegalutamide in patients with advanced prostate cancer, akhbar-sharq.com reports. The drug lowered a marker linked to disease activity, shrank some tumors and relieved pain in a number of patients akhbar-sharq.comakhbar-sharq.comakhbar-sharq.comOpen source ↗. The trial enrolled patients whose cancer had spread to other organs and was no longer held back by conventional hormone therapy akhbar-sharq.comakhbar-sharq.comakhbar-sharq.comOpen source ↗.

The study was led by Daniel Petrylak, professor of medical oncology and hematology at the Yale School of Medicine. The results were published in the Journal of Clinical Oncology akhbar-sharq.comakhbar-sharq.comakhbar-sharq.comOpen source ↗. Petrylak said the drug represents a new class of prostate cancer medicines because its mechanism differs from the treatments currently available akhbar-sharq.comakhbar-sharq.comakhbar-sharq.comOpen source ↗.

Mechanism: removing the hormone receptor

Standard therapy lowers testosterone, which feeds the growth of cancer cells, or blocks its action. Some tumors keep growing even when the hormone level falls akhbar-sharq.comakhbar-sharq.comakhbar-sharq.comOpen source ↗. The new drug instead targets the proteins that receive male hormones inside cancer cells and prompts the body to break them down and clear them out akhbar-sharq.comakhbar-sharq.comakhbar-sharq.comOpen source ↗.

The drug belongs to a recent class known as PROTAC. These compounds use a natural system inside cells to remove specific proteins that contribute to tumor growth, with the aim of cutting the signals that drive cancer cells to multiply akhbar-sharq.comakhbar-sharq.comakhbar-sharq.comOpen source ↗.

Trial results and genetic differences

In the first phase, the researchers tested the drug's safety. They concluded that a daily dose of 420 mg is suitable for patients who had already received treatment for advanced disease akhbar-sharq.comakhbar-sharq.comakhbar-sharq.comOpen source ↗.

In the second phase, the team tracked the effect by measuring prostate-specific antigen (PSA). This protein is secreted by the prostate gland, and a rise in blood levels indicates cancer activity and how the patient is responding to treatment. PSA fell in some participants. In others, soft-tissue tumors shrank and pain eased akhbar-sharq.comakhbar-sharq.comakhbar-sharq.comOpen source ↗.

The response was not uniform. The effect was clearer in patients whose tumors carried the T878 or H875 mutation than in those with other genetic changes akhbar-sharq.comakhbar-sharq.comakhbar-sharq.comOpen source ↗. The report notes that genetic testing of the tumor before treatment could show which patients benefit most. This fits the precision medicine approach, in which treatment is chosen according to the disease and each patient's genetic changes rather than being the same for everyone akhbar-sharq.comakhbar-sharq.comakhbar-sharq.comOpen source ↗.