Study uncovers promising therapeutic strategies against neuroendocrine prostate cancer

A new study has uncovered promising therapeutic strategies against one of the deadliest forms of prostate cancer.

McGill University researchers at the Rosalind and Morris Goodman Cancer Institute (GCI) identified a mechanism driving neuroendocrine prostate cancer, a rare and highly aggressive subtype for which there currently are no effective treatment options.

Findings published in Genes & Development show that prostate tumors in mice became more aggressive when the protein ERRγ was lost, while restoring its production in human cancer cells reversed this effect.

Prostate cancer is the most commonly diagnosed cancer among men in Canada. tumors that stop responding to hormone therapy evolve into neuroendocrine prostate cancer in about 15 per cent of patients, according to past research. After this shift, life expectancy typically falls below 18 months.

Therapy resistance remains one of the biggest challenges in cancer treatment, and prostate cancer is no exception. Our findings highlight ERRγ as a promising new therapeutic target."

Vincent Giguère, Lead Author, Professor, McGill's Department of Biochemistry and GCI researcher

Existing drugs show promise when ERRγ is lost

The researchers used advanced genetic and metabolic analysis to understand how losing ERRγ drives tumor growth. Their investigation revealed that two genes linked to cancer become overactive when ERRγ is missing.

As drugs that block these genes already exist for other cancers, the team tested two of them in mouse and human prostate cancer cells. When combined, the two drugs slowed the cancerous growth far more effectively than either drug alone.

"These findings have major clinical implications," said Giguère. "By targeting the genes that take over when ERRγ activity is low or lost, we open the door to new treatment strategies for patients who currently have few options."

Understanding why ERRγ function becomes impaired in the first place is still being investigated, he added.

Protein acts as brake on tumor progression

ERRγ, previously known for its role in energy metabolism, appears to act as a brake that prevents prostate cancer from advancing.

Preclinical findings led by first author Ting Li, a post-doctoral fellow in Giguère's lab, have revealed that neuroendocrine prostate cancers have much lower levels of ERRγ than other types of prostate tumors. Removing the protein in mice sped up tumor progression, while reactivating the protein in human prostate cancer cells reversed the process, confirming its protective effect.