HMN 2025: How New therapeutic strategies show promise against a hard-to-treat 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 ERR? 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% 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,” said lead author Vincent Giguère, Professor in McGill’s Department of Biochemistry and GCI researcher. “Our findings highlight ERR? as a promising new therapeutic target.”

Existing drugs show promise when ERR? is lost

The researchers used advanced genetic and metabolic analysis to understand how losing ERR? drives tumor growth. Their investigation revealed that two genes linked to cancer become overactive when ERR? 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 ERR? activity is low or lost, we open the door to new treatment strategies for patients who currently have few options.”

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

Protein acts as brake on tumor progression

ERR?, 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 ERR? 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.

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