Mutations in SPOP Protein Trigger Onset of Prostate Cancer Subtype, Study Finds

Mutations in SPOP Protein Trigger Onset of Prostate Cancer Subtype, Study Finds
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Mutations in a protein called SPOP trigger the development and growth of a subtype of prostate cancer, according to a study.

The findings may lead to treatments targeting the subtype, researchers said.

The study, “SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling,” was published in the journal Cancer Cell.

Nearly 10 percent of prostate cancer patients carry SPOP mutations, but the protein’s role in the development of the disease was not completely understood. Researchers at Weill Cornell Medicine found that SPOP mutations drive prostate cancer growth in a different way than other subtypes do.

Researchers used human prostate cancer samples and mice to investigate how mutant SPOP drives cancer growth. They discovered that the mutant protein activates two signaling pathways — the androgen receptor and PI3K pathways — that promote cancer cell survival and growth.

Normally the pathways balance each other out: When one is active, the other is not, so cells don’t grow out of control.

But in prostate cancers with SPOP mutations, they’re both active. “So, the fact that SPOP activates both pathways breaks the normal balance between the two, allowing cells to grow in an uncontrolled fashion,” Christopher Barbieri, the study’s senior author, said in a news release.

The findings may help scientists design better and more personalized treatments for both those who carry and do not carry SPOP mutations.

“This is important because now we have to think about SPOP cancers differently,” said Mark Rubin, another study author. “This may have implications for how people respond to treatment and how amenable they are to certain drugs.”

“This is a significant advancement for precision oncology,” added Howard Soule, the Prostate Cancer Foundation’s executive vice president and chief science officer. “Dr. Barbieri [and his] team have identified the molecular mechanisms by which SPOP gene mutations, which define one of the most frequently occurring prostate cancer subtypes, drive prostate cancer. This provides a roadmap for developing precision treatment strategies for patients with this tumor type, which may shift towards improved outcomes.”

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