Roswell Park-led scientists identify new defense mechanism against prostate cancer

A research team led by a scientist at Roswell Park Comprehensive Cancer Center has identified the molecule LRIG1 as an important endogenous tumor suppressor in prostate cancer. Writing in the journal Nature Communications, the team documents their findings from preclinical studies showing that overexpression of the LRIG1 protein inhibits prostate cancer development, while reducing naturally occurring LRIG1 promotes prostate tumor development.

Dean Tang, PhD, Professor and Chair of Pharmacology and Therapeutics at Roswell Park Comprehensive Cancer Center, is the senior author of the study, whose findings, he says, have compelled researchers to look at how best to incorporate LRIG1, a protein naturally expressed in patient tumor cells, into treatment for prostate cancer patients.

"Interestingly, the LRIG1 gene is induced in developing tumors, presumably representing the patient's defense mechanism against tumor growth. The LRIG1 expression levels in patients' tumors could potentially be developed into a prognostic biomarker — the higher the expression level, the better prognosis for prostate cancer patients.

Dr. Tang, Professor and Chair of Pharmacology and Therapeutics at Roswell Park Comprehensive Cancer Center

While the protein is not yet available as a therapeutic, Dr. Tang and team are working to develop it into an LRIG1-derived peptide, which, if those efforts are successful, could be used as anti-cancer therapeutic via intravenous injection.

This approach could potentially be an effective strategy for treating patients with inoperable prostate cancer. Prostate cancer is one of the most common and treatable types of cancer in men, with five-year survival rates reaching nearly 100% thanks to advances in detection and treatment.

However, prostate cancer remains the second-leading cause of male cancer deaths, because those with more advanced or aggressive forms of the disease eventually experience progression or recurrence despite treatment. Standard therapy uses drugs that target and block the androgen receptor (AR), a protein that binds to androgens (male hormones) to stop or inhibit prostate cancer cell growth. But the results often don't last, and many patients develop castration-resistant prostate cancer — an aggressive, treatment-resistant form of the disease — within a year of anti-androgen therapy.

"The good news for prostate cancer patients is that LRIG1 also possesses therapeutic efficacy and is actually up-regulated in tumors, in response to several oncogenic signals," notes Dr. Tang. "This new research represents a comprehensive exploration of LRIG1 expression, functions and mechanisms in prostate cancer, and advocates a novel conceptual paradigm that LRIG1 represents a pleiotropic-feedback tumor suppressor induced by multiple oncogenic signaling pathways."

Source:
Journal reference:

Li, Q. et al. (2019) LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer. Nature Communications. doi.org/10.1038/s41467-019-13532-4

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