New drug target to combat prostate cancer

May 25, 2018, University of Bern
Human adrenal cells that produce androgen precursors growing in the laboratory at the University of Bern. Credit: University of Bern

A study by an international team of researchers from University Children's Hospital Bern and the Autonomous University of Barcelona has discovered how the production of specific human sex hormones known as androgens is interrupted. These findings can help in development of new therapeutic approaches, as the overproduction of androgens is associated with many diseases including prostate cancer in men and polycystic ovary syndrome in women.

One in seven men in Europe are diagnosed with . While majority of cases are treated with surgical procedures and hormone therapy, in about 70'000 cases tumor growth continues even after surgical castration (castration-resistant cancer), where chemotherapeutic intervention is required.

One promising target has been the enzyme CYP17A1, which produces a precursor of androgens. Current treatment options include a drug called abiraterone. However, abiraterone has strong side effects and the life extension gained from treatment is only a few months.

Now a research team led by Amit Pandey from the Department of Pediatrics, Inselspital Bern and the Department for Biomedical Research of the University of Bern, in collaboration with Vall d"Hebron Research Institute in Barcelona, has reported a that damages the specific enzyme CYP17A1 which controls the production of androgens. The results of this study, published in the Open-Access Journal "Pharmaceuticals," could lead to a more efficient therapeutic approach for the treatment of castration-resistant prostate cancer. "Abiraterone, a CYP17A1 inhibitor, has been one the biggest breakthough drugs to combat advanced cancer. But resistance to this drug is still a major problem. Having a second line therapy as suggested by the current study, could be an effective way to control prostate cancer disease progression. This is a most exciting result," says Mark A Rubin, Director of the Department for Biomedical Reseach and Prostate Cancer Investigator.

Gene mutation prevents androgen production

Amit Pandey in Bern has been investigating how prostate cancer drugs work and found that the drug abiraterone changes many metabolic pathways. Collaborators in Barcelona, led by Dr. Laura Audi, identified a patient that had a loss of precursor. After genetic and biochemical laboratory tests, the Spanish team was able to confirm a novel mutation in the gene CYP17A1. "I immediately realized that this was not some ordinary mutation but is located at the center of CYP17A1 protein where bind," says Pandey.

Further studies in Bern showed that sex hormones could no longer attach properly at the center of the defective enzyme. Biochemical studies in Bern also found that mutated gene results in a defective CYP17A1 protein which is responsible for production of androgen precursor DHEA. Pandey hopes that knowledge from this study will lead to the development of better drugs for the treatment of prostate and .

Successful International teamwork in translational medicine

This research is an example of translational medicine showing the collaboration of the bedside to laboratory research. "This could not have been achieved by either team alone," Pandey emphasizes. The Audi group in Barcelona provided their decades of experience and competence in genetics and pathology and laboratories of Christa E Flück and Amit V Pandey at the University Children's hospital Bern used their experience in advanced recombinant protein production, molecular biology of sex steroids, and bioinformatics to understand the complexities of androgen production in humans. "These research results exemplify what can be achieved with close collaboration between multidisciplinary teams," says Pandey.

Explore further: Study uncovers an additional strategy for targeting treatment-resistant prostate cancer

More information: Mónica Fernández-Cancio et al. Mechanism of the Dual Activities of Human CYP17A1 and Binding to Anti-Prostate Cancer Drug Abiraterone Revealed by a Novel V366M Mutation Causing 17,20 Lyase Deficiency, Pharmaceuticals (2018). DOI: 10.3390/ph11020037

Related Stories

Study uncovers an additional strategy for targeting treatment-resistant prostate cancer

May 2, 2017
Prostate cancer cells depend on signaling through the androgen receptor (AR) to grow and survive. Many anti-cancer therapies that target ARs are initially successful in patients, including a class of drugs known as CYP17A1 ...

Researcher discovers metabolite of prostate cancer drug more effective at treating aggressive tumors

June 1, 2015
Cleveland: Cleveland Clinic researchers have discovered for the first time that a metabolite of an FDA-approved drug for metastatic prostate cancer, abiraterone (Abi), has more anti-cancer properties than its precursor. The ...

Team discovers similarities between next-generation prostate cancer drugs

June 22, 2017
Cleveland Clinic researchers have shown for the first time how a class of advanced prostate cancer drugs are processed in the body and how their anti-tumor activity might change depending on how they are metabolized. Their ...

Researchers find new gene variant linked to deadly prostate cancer

January 16, 2018
Cleveland Clinic researchers have confirmed for the first time a mechanistic link between the gene HSD17B4 and deadly, treatment-resistant prostate cancer.

Advanced prostate cancer treatment failure due to cell reprogramming

May 4, 2017
Columbia University Medical Center (CUMC) researchers have discovered a molecular mechanism that reprograms tumor cells in patients with advanced prostate cancer, reducing their response to anti-androgen therapy. The findings, ...

Study finds genetic mutation in castration-resistant prostate cancer

August 29, 2013
The mutation occurs in the androgen-synthesizing enzyme 3βHSD1 in castration-resistant prostate cancer (CRPC), according to research published online today in Cell. This mutation enables the tumor to make its own supply ...

Recommended for you

From the ashes of a failed pain drug, a new therapeutic path emerges

November 16, 2018
In 2013, renowned Boston Children's Hospital pain researcher Clifford Woolf, MB, BCh, Ph.D., and chemist Kai Johnsson, Ph.D., his fellow co-founder at Quartet Medicine, believed they held the key to non-narcotic pain relief. ...

Repurposing FDA-approved drugs can help fight back breast cancer

November 16, 2018
Screening Food and Drug Administration (FDA)-approved compounds for their ability to stop cancer growth in the lab led to the finding that the drug flunarizine can slow down the growth of triple-negative breast cancer in ...

Traditional chemotherapy superior to new alternative for oropharyngeal cancers

November 16, 2018
A drug increasingly used in combination with radiotherapy to treat a type of cancer that forms in the tonsils or the base of the tongue is inferior to a previously favored option, according to a large, clinical trial led ...

New 'SLICE' tool can massively expand immune system's cancer-fighting repertoire

November 15, 2018
Immunotherapy can cure some cancers that until fairly recently were considered fatal. In addition to developing drugs that boost the immune system's cancer-fighting abilities, scientists are becoming expert at manipulating ...

Anti-malaria drugs have shown promise in treating cancer, and now researchers know why

November 15, 2018
Anti-malaria drugs known as chloroquines have been repurposed to treat cancer for decades, but until now no one knew exactly what the chloroquines were targeting when they attack a tumor. Now, researchers from the Abramson ...

Standard chemotherapy treatment for HPV-positive throat cancer remains the most effective, study finds

November 15, 2018
A new study funded by Cancer Research UK and led by the University of Birmingham has found that the standard chemotherapy used to treat a specific type of throat cancer remains the most effective.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.