Prostate cancer drug shows additional promise, efficacy if taken differently

By Alex Lyda

After discovering a pathway that fuels prostate cancer, researchers at UT Southwestern Medical Center now have identified a second activity of a current Food and Drug Administration-approved drug that may be harnessed to combat advanced stages of the disease.

Nima Sharifi, M.D.

“Essentially, we have found that a drug used for metastatic prostate cancer may also hit a second tumor target if it is used in a different manner, potentially reversing drug resistance,” said Dr. Nima Sharifi, Assistant Professor of Internal Medicine and senior author of a study published in July in Clinical Cancer Research

Advanced prostate cancer usually regresses when the testosterone supply is cut off. This does not keep cancer from returning, however, because the tumors eventually make their own supply of androgens, becoming so-called “castration-resistant” prostate cancer. The drug, abiraterone acetate, normally works by blocking the enzyme CYP17A1, which is needed for tumors in the resistant state to make androgens. The block is incomplete, however, possibly allowing tumors to grow again.

In a prior study, Dr. Sharifi and a team of researchers narrowed the potential drug targets for advanced prostate cancer by demonstrating that late-stage tumors are driven by a different hormonal pathway. Building on that previous work, the most recent study shows that increased levels of abiraterone acetate block a second enzyme, 3ß-hydroxysteroid dehydrogenase, in this resistance pathway. The study also showed that growth of human prostate tumors in mice is deterred when this enzyme is blocked.

The drug is normally taken on an empty stomach. But giving the drug with food increases the amount of drug absorbed during digestion, resulting in higher levels in the blood. The new levels achieved in blood are high enough to block the second enzyme.

“This new way of administering abiraterone acetate now must be tested formally in clinical studies both for its potential therapeutic effect and the possibility of increased toxicity,” Dr. Sharifi said.

Dr. Sharifi’s work was funded by the Howard Hughes Medical Institute, the Prostate Cancer Foundation, the American Cancer Society, and the Department of Defense.

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