Cellular Signature Identifies Patients with Treatment Resistant Prostate Tumors

Prostate cancer treatment often includes androgen receptor pathway inhibitors (ARPIs) like enzalutamide. While many patients respond well to ARPIs, about one-third do not experience significant benefit, even when treated with these drugs. These “extreme non-responder” patients progress more quickly and have a much shorter survival time. This issue has been challenging in clinical practice, as identifying why some tumors respond poorly and finding ways to improve their treatment has remained unclear. Now, a new study has uncovered a cellular signature linked to this poor response, offering a potential new approach for improving treatment outcomes in these patients.

Researchers at the University of Michigan Rogel Cancer Centre (Ann Arbor, MI, USA) focused on identifying a gene program associated with extreme non-response to ARPIs in prostate cancer patients. They analyzed RNA sequencing data and clinical outcomes from several prostate cancer clinical trial datasets. The study revealed that the chemotherapy drug docetaxel, typically given later in treatment, could be beneficial earlier for patients whose tumors harbor the ARPI extreme non-response program. In addition to this, the researchers discovered that the kinase CDK2 regulates this gene program, suggesting that targeting CDK2 could block the program and reduce tumor growth.

The findings, published in npj Precision Oncology, showed significant differences in gene expression between prostate cancers that responded well to ARPIs and those that did poorly. The research suggests that patients with the extreme non-response program might benefit from earlier docetaxel treatment, offering a new way to manage treatment for this subset of patients. Additionally, the researchers propose that CDK2 inhibitors, already being tested in clinical trials for other cancers, could offer a new avenue for treating prostate cancers with this extreme non-response program. The team plans to continue exploring this potential, with the goal of developing more effective treatment strategies for advanced prostate cancer patients.

“We found significant differences in the gene expression program between prostate cancers that do exceptionally well vs. exceptionally poorly with ARPIs,” said investigator Anbarasu Kumaraswamy, Ph.D. “Patients who have this extreme non-response program appear to get significant benefit from docetaxel, suggesting these patients may be good candidates for earlier docetaxel treatment.”

Related Links:
U-M Rogel Cancer Centre