How prostate cancer is resistant to treatment

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Destination Health: Dr. Manny talks about the risk factors and symptoms of prostate cancer

It is the second most frequently diagnosed cancer in men, just behind skin cancer.

It is usually slow growing and there are lifesaving treatments available.

But, sometimes the cure can prostate cancer more deadly.

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


Hormones called androgens stimulate prostate cancer cells to grow. Newly developed anti-androgen therapy for prostate cancer are a major step forward 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 these cells shrink or grow more slowly.

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

In their study, researchers analyzed tissue samples of men with NEPC and prostate cancer cell lines and a mouse model of NEPC made by the researchers.

She said that she discovered a molecular “switch” for the activation of this form of cancer for the treatment of drug-resistant after anti-androgen treatment.

The creation of drug-resistant forms of cancer

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

That is no longer the case. It is now almost 30 percent.

“Things have changed a lot by the new generation of androgen inhibitors, which are much stronger than the former,” Diaz-Meco noted.

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

“But these treatments can also lead to the cancer to become resistant, like bacteria develop resistance to antibiotics,” Diaz-Meco said. “The incidence of these neuro-endocrine tumors after a 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 benign tissue in the prostate.

The test can detect high levels of PSA that may indicate prostate cancer, but the treatment-resistant forms of cancer, it may sometimes occur that they are detected.

“The problem with this new, drug-resistant cancer cells is that they are androgen indifferent, or androgen-independent, that is the reason why the treatments stop working and why aren’t they increasing PSA levels,” said Diaz-Meco.

Undetected, the cancer will eventually move on to other places, mostly in the liver, lungs and bones.

A surprising discovery

Although there is no cure for NEPC, Diaz-Meco, the research could eventually lead to new treatment options.

She stresses that her focus is now on finding a way to “awaken a certain way, the androgen receptor path” NEPC tumors more detectable and treatable.

“Our initial observation working with a kinase (an enzyme that is required for certain cell processes) the so-called atypical protein kinase C was surprising,” she said. “The tumors were completely due to the lack of the presence of this protein; usually tumors show high amounts of this kinase.”


She thinks that this discovery may lead to a new treatment, that can make this form of cancer is vulnerable to anti-androgen therapy.

Early detection is the best defense

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

“However, there is nothing a man can do to prevent prostate cancer,” Wenske told healthline. “Early detection is the key. And although there is much controversy about the use of PSA as a prostate cancer screening marker, patients, especially those with a higher risk, should definitely seek out a urologist who will carry out an ‘intelligent’ screening for prostate cancer.”

Intelligent screening includes testing for biomarkers in addition to PSA, to improve the screening accuracy.

Wenske said that this is because “PSA can be influenced by many factors, so instead of looking at PSA as a number, but indicates that the risk of cancer across a continuum. For example, some men with a PSA level lower than 4 ng/ml would be abnormal, but in other patients a PSA of more than 4 ng/ml would be acceptable.”


He explained that additional testing can be helpful in determining who should undergo a prostate-MRI, followed by a prostate biopsy, to know which patient has significant prostate cancer that should be treated.

“When localized prostate cancer is discovered and treated, the success is very good,” Wenske said.

The bottom line

Prostate cancer, when caught early, can be cured. Powerful new treatments that have anti-androgen therapy will stop tumor growth and even shrinkage.

But, this is the same therapy can make the treatment-resistant prostate cancer that will spread.

New research has shown how this form of cancer is resistant. It can point the way to new anti-androgen treatments that the disease is treatable.

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