Prostate cancer: How it becomes resistant to treatment

Researchers say they may have unlocked the mystery of resistant prostate cancer. They hope it’ll lead to better treatments.

| The Independent | It’s the second most diagnosed cancer in men, just behind skin cancer.

It’s typically slow growing and there are life-saving treatments available.

But, sometimes the cure can make prostate cancer more deadly.

A new study released recently from Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California, details how prostate cancer can be transformed into an aggressive and incurable disease — by the treatment that’s supposed to save lives.

Hormones called androgens stimulate prostate cancer cells to grow. Newly developed anti-androgen therapies for prostate cancer are a major advance in the fight against this disease.

Testosterone and dihydrotestosterone (DHT) are the main androgens in men. Lowering androgen levels or stopping them from getting into prostate cancer cells can make those cells shrink or grow more slowly.

However, men who receive these new treatments are also more likely to develop a deadly, treatment-resistant cancer called neuroendocrine prostate cancer (NEPC). There are no effective treatments for this type of cancer.

In their study, researchers analysed tissue samples from men with NEPC as well as prostate cancer cell lines and a mouse model of NEPC created by the researchers.

They said they discovered a molecular “switch” that triggers this cancer to become treatment-resistant after anti-androgen treatment.

Creating resistant cancers

NEPC previously accounted for only 2 to 5 percent of all diagnosed prostate cancer cases, according to Dr. Maria Diaz-Meco, a professor in the Cancer Metabolism and Signaling Networks Program at Sanford Burnham Prebys Medical Discovery Institute and lead author of the study.

That’s no longer the case. It’s now approaching 30 percent.

“Things have changed a lot due to the new generation of androgen inhibitors, which are much more potent than earlier ones,” Diaz-Meco noted.

The androgen treatments have increased survival against tough-to-treat prostate cancer as well as those where tumors have spread.

“But these treatments can also cause cancers to become resistant, like bacteria develop antibiotic resistance,” Diaz-Meco said. “The incidence of these neuroendocrine tumors after targeted treatment is now much higher.”

NEPC is undetectable by PSA test

The PSA test is a blood test used to screen for prostate cancer. PSA is a protein produced by both cancerous and noncancerous tissue in the prostate.

The test can detect high levels of PSA that may indicate prostate cancer, but the treatment-resistant cancers can sometimes avoid detection.

“The problem with these new, resistant cancer cells is that they’re androgen indifferent, or androgen independent, which is why the treatments stop working and why they don’t increase PSA levels,” said Diaz-Meco.

Undetected, the cancer will eventually move to other places, usually the liver, lungs, and bone.