PTEN Loss In Prostate Cancer: What Patients Should Know

“PTEN is a protein that most cells have … It basically helps stop the cell from growing and dividing. Unfortunately in cancer cells, sometimes that gene that makes that protein is lost — and we call this PTEN loss,” Dr. Stephen Freedland, a urologist at Cedars-Sinai, tells SurvivorNet.

Essentially, PTEN is a gene that acts like a brake inside your cells. Under normal circumstances, this gene produces a protein that helps keep cell growth in check. It prevents cells from dividing too quickly or uncontrollably.

When PTEN is working normally, it helps protect against cancer. But when PTEN is lost or turned off, that brake disappears. PTEN loss may occur up to 40-50% of metastatic castration-resistant prostate cancers (mCRPC).

Why PTEN Loss Matters

Not all prostate cancers behave the same way. Some grow slowly and may never cause serious problems. Others are more aggressive and require more intensive treatment. PTEN loss is one of the factors that can help distinguish between these two patterns.

“We know tumors that have lost this PTEN tend to be more aggressive. It’s something we’re looking at in prostate cancer and we actually see, particularly in patients with higher risk disease and metastasis at diagnosis,” Dr. Freedland explains.

That means that cancers with PTEN loss tend to grow faster and are more likely to spread beyond the prostate. They may also respond less predictably to standard therapies.

For patients, that doesn’t mean things are hopeless, but it does mean the disease may need to be approached differently.

Treatment & Testing For PTEN Loss

In June 2026, the first targeted therapy was approved to treatment patients with PTEN loss. A drug called Truqap (capivasertib) was approved in combination with abiraterone and prednisone for patients with metastatic hormone-sensitive prostate cancer (also known as androgen pathway modulation-naïve or sensitive).

However, up until Truqap’s approval, there was no targeted approach to treat prostate cancers that have this specific characteristic.

So even when PTEN loss was detected, it did not always change immediate treatment decisions, especially in patients with earlier-stage disease who are already expected to do well with standard therapies.

PTEN testing is more commonly considered in patients with advanced or metastatic cancer, where understanding the biology of the tumor may have a greater impact on how aggressively doctors choose to treat it. That may change now.

While PTEN clearly tells doctors something important about tumor behavior, “we don’t routinely test for it” yet, Dr. Freedland explains, largely because a direct therapy was lacking previously.

The approval was based on results from the phase III clinical trial, the CAPItello-281 trial, which evaluated whether capivasertib (Truqap) could be an option for patients with PTEN deficiency.

Clinical Trials: An Important Option

When standard treatments stop working, clinical trials may offer additional options.

Clinical trials test new therapies or new combinations of treatments that are not yet widely available. They are often the first option doctors consider when patients have exhausted existing treatments.

Many of the therapies available today, including immunotherapy and targeted therapy for prostate cancer, became possible because patients participated in earlier clinical studies. Those trials helped researchers understand how to harness the immune system to fight cancer.

Today’s clinical trials continue to explore new strategies, including:

• New immunotherapy drugs
• Combination therapies
• Personalized treatments targeting specific tumor characteristics

For some patients, clinical trials provide access to promising therapies years before they become widely available.

If you want to participate in a clinical trial, your first step should be to talk with your doctor. They can address many of your initial questions and help you determine if you are eligible.

The next step is finding the right trial for you.

SurvivorNet has a resource to help with this called the Clinical Trial Finder.

Questions To Ask Your Doctor

• Have I/can I undergo molecular testing?
• What specific mutations will you be testing for in my tumor?
• How will the results of this testing affect my treatment options?
• Am I eligible for any targeted therapies based on my molecular testing results?

Learn more about SurvivorNet's rigorous medical review process.

---