Prostate cancer discovery could improve precision therapy

Volume 6, Issue 4, 2017

Summary

Researchers found that SPOP mutations stabilize BET proteins against the action of BET inhibitors.

Haojie Huang, Ph.D.

Haojie Huang, Ph.D.

Mayo Clinic researchers have identified a new cause of treatment resistance in prostate cancer, a finding that also suggests ways to improve prostate cancer therapy.

The prostate cancer findings were published in a paper in Nature Medicine in September 2017.

In the paper, the Mayo Clinic researchers explain the role of mutations within the SPOP gene in the development of resistance to one class of drugs. SPOP mutations are the most frequent genetic changes seen in primary prostate cancer. These mutations play a central role in the development of resistance to drugs called bromodomain and extra-terminal domain (BET) inhibitors.

BET inhibitors are drugs that prevent the action of BET proteins. These proteins help guide the abnormal growth of cancer cells.

"As a therapy, BET inhibitors are promising, but drug resistance often develops," said Haojie Huang, Ph.D., senior author of the Nature Medicine paper and a Mayo Clinic molecular biologist in Rochester, Minnesota.

Prostate cancer is among the most diagnosed malignancies in the United States. It is also the third leading cause of cancer death in American men, according to the American Cancer Society. Because of this, Dr. Huang said, improving treatments for prostate cancer is an important public health goal.

In the Nature Medicine paper, the authors report that SPOP mutations stabilize BET proteins against the action of BET inhibitors. By this action, the mutations also promote cancer cell proliferation, invasion and survival.

"These findings have important implications for prostate cancer treatment," Dr. Huang said, "because SPOP mutation and elevated BET protein expression can now be used as biomarkers to improve the outcome of BET inhibitor-oriented therapy of prostate cancer with SPOP mutation or BET protein overexpression."