New Therapy for Aggressive Prostate Cancer Improves Survival | National Cancer Center, Inc.

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New Therapy for Aggressive Prostate Cancer Improves Survival | National Cancer Center, Inc.

By NantionalCC

2-3 minutes

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There is some very good news on the prostate cancer front.

According to an article in the New York Times on June 25, 2021, a new therapy for aggressive prostate cancer has been developed that will increase survival rates. It relies on a radioactive molecule to target a protein found on the surface of prostate cancer cells.

This new targeted therapy drives radiation straight to the cancer itself, and the place where the cancer “lives,” without damaging surrounding tissue.  It may have applications for the treatment of other cancers. 

“This represents an exciting and significant advancement in the treatment of prostate cancer,” said Regina English, Executive Director of the National Cancer Center. “It is just the type of progress we hope to help fund with our new Prostate Cancer Project.”

Prostate cancer is the second-leading cause of cancer death among American men, after lung cancer; an estimated 34,130 men will die of prostate cancer this year. One in eight men will be diagnosed with the disease at some point in their lives. The risk increases with age, and the cancer is more common in Black men.

Last year the National Cancer Center (NCC) launched the Prostate Cancer Project.  NCC awarded its first $40,000 of a two-year grant in 2021-22 to Varadha B Venkadakrishnan, Ph.D. at the Dana-Farber Cancer Institute, Boston, MA. With substantial progress demonstrated, Varadha will receive a second grant for $42,000 next year. NCC increased its grant monies in 2021-22 by 21%, to a total of $658,000.

Varadha’s project studies treatment resistance to anti-androgen hormone therapies whereby cancer cells change their “identity” and start to look less and less like cancer cells; a process called “lineage plasticity.”  This project will define the mechanisms underlying “lineage plasticity” in order to develop novel therapeutic interventions to block or reverse treatment resistance in prostate cancer.

• July 17, 2021
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 Treating advanced prostate cancer typically involves castration – to reduce levels of testosterone, which fuels the growth of tumors – or giving drugs that blockade the androgen receptor (AR), which responds to testosterone by stimulating cancer-growth genes.

While these measures can keep the disease at bay initially, resistance almost always occurs as the androgen receptor becomes re-activated and resumes signaling the tumor-growth genes, even when testosterone levels have been dramatically reduced. This condition is known as castration-resistant prostate cancer, and there is currently no curative therapy. A number of “next-generation” androgen pathway blockers have been developed and are in use, but in all cases resistance occurs.

Now, aiming to discover new targets for blocking androgen receptor activity, a Dana-Farber-led team has identified a critical regulator of AR signaling that prostate cancer cells depend on, according to their publication in Cell Reports.

In the laboratory, they showed that inhibiting this regulator – a protein called PRMT1 – reduced androgen receptor activity and blunted its effect on cancer genes that whose expression was elevated by the AR receptor. Furthermore, inhibiting PRMT1 slowed the growth of several types of prostate cells in which the androgen receptor was active.

“These results suggest that the growth-inhibitory effects of PRMT1 inhibition in prostate cancer cells are specifically mediated through the AR axis,” say the researchers, led by Srinivas Viswanathan, MD, PhD, a genitourinary oncologist at Dana-Farber, and Peter Choi, PhD, of the University of Pennsylvania. Furthermore, the scientists say that “AR-driven prostate cancer cells are uniquely susceptible to combined AR and PRMT1 inhibition. Our findings implicate PRMT1 as a key regulator of AR output and provide a preclinical framework for co-targeting of AR and PRM1 in advanced prostate cancer.”

The researchers identified PRMT1 as a key regulator of AR expression by carrying out genome-wide genetic (CRISPR) screening of a cellular model of advanced prostate cancer. This screening uncovered PRMT1 as a critical mediator of AR expression and signaling that is required for the androgen receptor to bind to its genomic target sites.

The scientists noted that these laboratory-based findings could lead to the development of strategies to target AR and PRMT1 in treating advanced prostate cancer. This approach has not yet been tested in human studies, but several PRMT inhibitor drugs are being investigated in clinical studies.