New Study Identifies Gene Program That May Explain Why Some Prostate Cancers Don't Respond to Treatment

A new study identified a cellular signature that may explain why around one third of prostate cancers respond poorly to treatment.

Androgen receptor pathway inhibitors (or ARPI) like enzalutamide are standard of care for advanced prostate cancer. Many patients will have a “long term good response to the drugs, [but] some will derive no benefit whatsoever.” Patients who do not respond to the drugs, termed “extreme non-responders,” die much more quickly than those who do.

The researchers involved with this study “identified a gene program linked to ARPI extreme non-response” and “discovered the chemotherapy docetaxel could be a good option earlier on in patients whose tumor harbors the ARPI extreme non-response program.” Docetaxel is approved in prostate cancer treatment but is “typically given later in the course of treatment.” Thus, patients whose tumors do not respond to ARPI treatment “may be good candidates for earlier docetaxel treatment.”

The researchers also found that “the kinase CDK2 regulates the extreme non-response program, and targeting CDK2 could block the program and reduce tumor growth in the laboratory samples that harbored the ARPI extreme non-response program. The authors suggest exploring CDK2 inhibitors, currently in clinical trials in other cancer types, as a promising new direction in prostate cancers.”