Scientists at the University of Michigan Rogel Cancer Center have found an important clue to why some men with advanced prostate cancer don’t respond to a common treatment.
About one in every three prostate cancer patients doesn’t benefit from a standard drug called enzalutamide.
These men often get worse much faster than others, and their cancer is harder to treat. The new research may help doctors choose better treatments for them earlier on.
Prostate cancer is one of the most common cancers in men. In advanced stages, it’s often treated with drugs that block male hormones, especially one called androgen.
These hormones help prostate cancer grow, so stopping them can slow the disease down.
One common medicine used to block these hormones is enzalutamide, which belongs to a group of drugs called ARPIs, short for “androgen receptor pathway inhibitors.”
For many patients, ARPIs can work well and keep the cancer under control for a long time. But unfortunately, some men don’t get any benefit at all from them. Doctors have called these patients “extreme non-responders.” Their cancers seem to ignore the drug completely, and the disease progresses much faster than usual.
To understand why this happens, the research team looked at genetic data from men in prostate cancer clinical trials. They studied the RNA, which is like a working copy of genes that shows what a cell is doing.
By analyzing the RNA patterns, they found that tumors in extreme non-responders had a special “signature” – a group of genes that behave differently from those in men who responded well to ARPIs.
The study was led by Dr. Anbarasu Kumaraswamy, a scientist in the Alumkal Lab. He and his team discovered that this gene signature could explain why ARPIs fail in these patients. The tumors with this signature seemed to be wired in a different way, which made them resist the treatment.
However, the researchers also found some hope. Another cancer drug, called docetaxel, which is a type of chemotherapy, seemed to work better in patients with the non-responder gene signature.
Docetaxel is already used to treat prostate cancer, but usually much later, after ARPIs stop working. This study suggests that for some patients, starting docetaxel earlier could help slow the disease more effectively.
In the lab, the team also discovered something else: a protein called CDK2 seems to control the non-responder gene program. When they blocked CDK2 in cancer cells, the tumors grew more slowly.
This means CDK2 could be a new target for treatment, especially for those patients whose cancer won’t respond to standard hormone-blocking drugs. Some drugs that block CDK2 are already being tested for other cancers, so they might be used for prostate cancer in the future too.
In summary, this study offers two big takeaways. First, it shows that we can now identify which patients are unlikely to benefit from ARPI drugs by checking their tumor’s gene activity.
Second, it gives doctors new ideas about what to do next — like using docetaxel earlier or testing drugs that block CDK2. This kind of personalized treatment approach could help men with aggressive prostate cancer live longer and get more effective care.
By revealing the hidden gene program behind poor drug response, this research brings us one step closer to matching each patient with the treatment that works best for them.
If you care about prostate cancer, please read studies about 5 types of bacteria linked to aggressive prostate cancer, and new strategy to treat advanced prostate cancer.
For more information about prostate cancer, please see recent studies about new way to lower risk of prostate cancer spread, and results showing three-drug combo boosts survival in metastatic prostate cancer.
The research findings can be found in npj Precision Oncology.
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