A silent genetic switch could explain why some prostate cancers become lethal — and now, researchers have found a way to flip it back.
Key Points at a Glance
- Researchers identified PROX1 as a key early driver of aggressive prostate cancer
- PROX1 becomes highly active as tumors lose androgen receptor dependence
- Blocking PROX1 causes cancer cells to die — even in treatment-resistant forms
- HDAC inhibitors, already FDA-approved, can suppress PROX1 activity
- This reveals a promising treatment route for lethal prostate cancer subtypes
Prostate cancer isn’t always the slow, manageable disease it’s known to be. In some patients, tumors undergo a dangerous transformation — shedding their dependency on the androgen receptor, the key target of most current therapies. These cancers become aggressive, untreatable, and often lethal. Now, scientists have pinpointed a gene that may be driving that shift — and they’ve found a way to shut it down.
A team at the University of Michigan Rogel Cancer Center discovered that the gene PROX1 becomes highly active as prostate tumors transition into more aggressive, treatment-resistant forms. In a new study published in the Journal of Clinical Investigation, researchers showed that PROX1 acts like a master regulator, suppressing the androgen receptor and flipping the tumor’s identity — a process called lineage plasticity.
“We think PROX1 may be pulling the strings,” said lead author Dr. Joshi Alumkal. “It helps tumors change their playbook and break away from the controls of standard therapies.”
In patient tumor biopsies, PROX1 was the top upregulated gene in cancers that had undergone this identity shift. The more aggressive the tumor, the higher the PROX1 levels — especially in double-negative and neuroendocrine prostate cancers, two of the deadliest subtypes.
Crucially, when the team genetically deleted PROX1 from these tumors in lab experiments, the cancer cells stopped growing and died. That’s when they asked: Could existing drugs do the same thing?
Enter HDAC inhibitors — a class of FDA-approved drugs already used in other cancers. When researchers treated PROX1-positive prostate cancer cells with these inhibitors, something remarkable happened: PROX1 protein levels dropped, and the tumors shrank, mirroring the effects of a full genetic knockout.
“It’s like cutting the power supply to a rogue machine,” said Alumkal. “These HDAC inhibitors indirectly target PROX1 by disrupting its molecular partners.”
This breakthrough offers a beacon of hope for patients facing one of the most deadly forms of prostate cancer. Currently, there are few treatment options once a tumor abandons its reliance on the androgen receptor. The new findings point to a potential clinical strategy — repurposing existing drugs to take out the tumor’s new master switch.
The next step: human trials. With a range of HDAC inhibitors already approved, researchers hope to fast-track this approach into clinical testing. If successful, it could redefine how we treat advanced prostate cancer — not by chasing the tumor’s every move, but by turning off its ability to transform.
Source: Michigan Medicine
Enjoying our articles?
We don’t show ads — so you can focus entirely on the story, without pop-ups or distractions. We don’t do sponsored content either, because we want to stay objective and only write about what truly fascinates us. If you’d like to help us keep going — buy us a coffee. It’s a small gesture that means a lot. Click here – Thank You!
