Novel biological markers may help predict which patients will benefit most from specific therapies to treat prostate cancer, according to a study published in the journal Cell.
The discovery has the potential to transform treatment strategies for advanced cases of prostate cancer, said Edward Schaeffer, MD, PhD, the chair and Harold Binstein Professor of Urology, who was a co-author of the study.
“This is a coming-of-age for precision medicine in the field of prostate oncology,” said Schaeffer, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “Clinical-grade transcriptomic profiling of prostate tumors can help us gain insights into the responsiveness of a cancer to different therapies. This has a lot of potential power to enhance the precision with which we deploy a variety of treatments for prostate cancer.”
The study, which analyzed tumor samples from over 1,500 patients enrolled in previous clinical trials, found that specific genetic and protein-based signatures are strongly associated with long-term survival outcomes. These trials tested two widely used therapies—docetaxel, a chemotherapy drug, and abiraterone, a hormone therapy.
One of the key findings is that tumors with active androgen receptor signaling—a pathway involved in regulating male hormones—were linked to longer survival, while tumors that grow and divide rapidly were associated with poorer outcomes.
The study also validated a previously known biomarker, called the Decipher RNA signature, as predictive of survival benefit from docetaxel in patients with metastatic prostate cancer. This means that a genomic test could help identify which patients are likely to respond well to chemotherapy, Schaeffer said
Another significant discovery involved the PTEN gene, a tumor suppressor often absent in aggressive cancers. Using transcriptome-based classifiers, investigators observed that tumors with PTEN inactivation were more likely to show protein loss and metabolic disruption. These cancers tended to respond poorly to hormone therapies but showed increased sensitivity to docetaxel, suggesting a potential shift in treatment approach for these patients, Schaeffer said.
“This study establishes that it’s possible for us to use these next-generation predictive biomarkers to customize therapies for patients with prostate cancer,” Schaeffer said.
With further validation, these biomarkers could become part of routine care, offering hope for improved outcomes in a disease that remains one of the leading causes of cancer death among men.
Building on the study, Schaeffer and his collaborators globally will continue to investigate how male hormone signaling impacts the responsiveness of tumors to chemotherapy.
“Our next steps will be to identify predictive signatures that help us design optimized androgen receptor therapies, including the extent and duration of treatments,” Schaeffer said.
The study was supported by funding from Prostate Cancer UK, the National Institutes of Health (R01CA238020) and the Department of Defense under grant W81XWH-19-PCRP-EIRA PC190530 PAIR.
