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PCF Young Investigators in Ireland are researching molecular differences between aggressive and low Gleason-grade cancers

From its inception, PCF has focused heavily on investing in human capital, particularly in the form of young scientists with innovative approaches and tenacity. Our support of 125 young investigators around the world since 2008 underscores this commitment.

One of the biggest challenges in diagnosing and treating the more than 27 known varieties of prostate cancer is discerning between the most aggressive forms of this cancer, varieties that represent intermediate levels of aggressiveness, and those that are indolent, or non-life-threatening. The ability to distinguish between these would greatly reduce overtreatment, sparing men from the side effects of treatment, and enable us to deliver personalized treatments that are best suited to a specific genotype or variety.

Two of PCF’s newest Young Investigators, the first ever in Ireland, are working on this very problem at Trinity College in Dublin.

Antoinette Perry, PhD, at Trinity College’s Institute of Molecular Medicine—using an award sponsored by The Handler Family Fund—is working to address the critical, unmet need of identifying aggressive tumors at an early stage while they are potentially curable and distinguishing them from indolent, low-grade tumors which can be treated with proactive surveillance to avoid overtreatment of clinically insignificant disease. To this aim, Dr. Perry is studying the chemical modifications to DNA’s outer shell, known as epigenetics.

Prostate cancer is driven by several epigenetic alterations and genetic abnormalities. Epigenetic alterations can be detected non-invasively with high sensitivity in peripheral blood and urine. Therefore, detecting prostate cancer-specific epigenetic alterations holds potential for both improved prostate cancer diagnostics and patient risk stratification. Dr. Perry is developing new blood and urine biomarkers for the non-invasive detection of aggressive prostate cancer. Dr. Perry’s goal of identifying epigenetic patterns of DNA alterations that are specifically associated with aggressive prostate cancers holds promise for alleviating the burden of overtreatment for indolent disease.

Another PCF Young Investigator at Trinity College’s Institute of Molecular Medicine is Stephen Finn, MBBS, PhD, sponsored by PCF donor Steve Wynn. Genetic information flows outward from our genes on DNA as follows: gene (DNA) to RNA to protein. This sequence of genetic transcription is known as the Central Dogma. RNAs, the products of DNA, either give rise to proteins called coding RNAs or non-coding RNAs. Despite their name, non-coding RNAs (ncRNAs) are functional molecules that perform specialized roles in the cell, such as regulation of gene expression. Recent reports have provided evidence for the role of small, non-coding RNAs in the development and progression of prostate cancer.

Dr. Finn proposes to identify those non-coding RNAs that are associated with aggressive prostate cancer as defined by failure to respond to Androgen Deprivation Therapy (ADT), disease-specific mortality and other factors. His research will identify the role of non-coding RNAs in aggressive prostate cancer and correlate these to prostate cancer-specific outcomes, laying the groundwork for the design of new therapeutics that will target specific non-coding RNAs.

These studies may provide reliable biomarkers of aggressiveness which can help in patient stratification for treatment and more efficient disease monitoring.