涩里番

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

涩里番 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.

show that prostate tumours in mice became more aggressive when the protein ERR纬 was lost, while restoring its production in human cancer cells reversed this effect.

Prostate cancer is . Tumours 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.

鈥淭herapy resistance remains one of the biggest challenges in cancer treatment, and prostate cancer is no exception,鈥� said lead author Vincent Gigu猫re, Professor in 涩里番鈥檚 Department of Biochemistry and GCI researcher. 鈥淥ur findings highlight ERR纬 as a promising new therapeutic target.鈥�

Existing drugs show promise when ERR纬 is lost

The researchers used advanced genetic and metabolic analysis to understand how losing ERR纬 drives tumour growth. Their investigation revealed that two genes linked to cancer become overactive when ERR纬 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.

鈥淭hese findings have major clinical implications,鈥� said Gigu猫re. 鈥淏y targeting the genes that take over when ERR纬 activity is low or lost, we open the door to new treatment strategies for patients who currently have few options.鈥�

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

Protein acts as brake on tumour progression

ERR纬, 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 Gigu猫re鈥檚 lab, have revealed that neuroendocrine prostate cancers have much lower levels of ERR纬 than other types of prostate tumours. Removing the protein in mice sped up tumour progression, while reactivating the protein in human prostate cancer cells reversed the process, confirming its protective effect.

About the study

鈥� by Ting Li and Vincent Gigu猫re et al., was published in Genes & Development. The study was conducted in collaboration with Prof. Jin-Jian Lu of the University of Macau and supported by the Canadian Institutes of Health Research, the Terry Fox Research Institute, the Cancer Research Society, Fonds de Recherche du Qu茅bec 鈥� Sant茅 and D茅fi Canderel.