How prostate cancer becomes resistance to treatment

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

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 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 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.

Diaz-Meco added that the incidence of these neuroendocrine tumors after targeted treatment is now much higher.

Early detection is best defense

“In general, for prostate cancer, there are two big risk factors,” said Dr. Sven Wenske, urologist and assistant professor of urology at Columbia University Irving Medical Center in New York. “One is ethnicity. For example, African-American men have a significantly higher risk of developing prostate cancer than white men. The other one is a family history of prostate cancer, particularly in a father or paternal uncle, paternal grandfather, or brothers, especially when the disease in those relatives occurred at a younger age.”

However, there is nothing a man can do to prevent prostate cancer. 

Early detection is key, while there is a lot of controversy about using PSA as a prostate cancer screening marker, patients, especially those at higher risk, should certainly seek out a urologist who will perform an ‘intelligent’ prostate cancer screening,” Wenske said.