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Faces of Prostate Cancer

Dr. Muneesh Tewari

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Nestled in the Pacific Northwest, the Seattle area has a growing group of cancer researchers uniquely engaged in the quest to end prostate cancer as a health risk for men and their families. Lending their time and expertise in the area of prostate cancer, PCF- funded researchers Drs. Peter Nelson and Robert Vessella from the University of Washington are currently working in collaboration with Dr. Muneesh Tewari of the Fred Hutchinson Cancer Research Center.

Several PCF-funded researchers including: Drs. Norman Greenberg, Paul Lange, Beatrice Knudsen, Alvin Liu, and Janet Stanford from the University of Washington and Fred Hutchinson Cancer Research Center have also help created the perfect collaborative environment for the advancement of prostate cancer research.

In the last three years, Dr. Tewari has expanded his research efforts to prostate cancer by applying his vast knowledge of microRNA (miRNA) to microRNA-based diagnostics and targeted therapeutics for the disease.

"We speculate that there may be microRNA profiles in the blood that predict whether a tumor will respond to specific treatment," says Dr. Tewari. "In the future, we might also be able to monitor patient responses to cancer treatment through microRNA profiles expressed in the blood."

The study of miRNA and its relation to cancer is relatively new to the world of science. Originally discovered by scientists in the 1990's, miRNAs are short, single-stranded RNA molecules that play a critical role in controlling gene activity. It is postulated that one miRNA molecule could possibly regulate hundreds of genes in a person's body.

Given the regulatory nature of miRNA, scientists have sought to find what its connection is to the development of tumor cell progression. Dr. Tewari's research specifically looks to uncover why the regulation by these molecules breaks down, allowing for unchecked cancer cell growth. In addition, his team has made the surprising discovery that miRNAs from prostate cancer enter the bloodstream where they can be detected as cancer-associated biomarkers.

In October of 2008 Dr. Tewari shared his latest scientific findings at the PCF's 15th Annual Scientific Retreat, detailing his discovery of one specific cancer-associated microRNA: miR-141. In particular, miR-141 levels measured in a patient's blood were elevated in a large fraction of patients with metastatic prostate cancer. Although much more work needs to be done to study this marker at various stages of disease, it is possible that miR-141 could provide additional information regarding the cancer beyond what is currently possible with existing biomarkers like the PSA test (prostate-specific-antigen test).

A common concern with PSA test results is the well-established effect of hormone levels on natural PSA production. This fact makes it difficult to determine whether PSA level changes in men undergoing hormone therapy are due to changes in tumor behavior – or simply a side effect of therapy. Based on current knowledge, it is expected that miR-141 levels will be independent of hormone levels – suggesting the microRNA may make for a more accurate biomarker of tumor activity in some situations.

"The advantage of using microRNA is that these molecules are extremely stable in blood samples," said Dr. Tewari. "If we can identify microRNAs that are specific to prostate cancer, then this might add significantly to current markers such as PSA for diagnosis and prognosis of the disease."

Based on this deduction, Dr. Tewari has developed a blood test in his laboratory that measures miR-141 in human blood samples. His intention is to apply the test in clinical studies – investigating the utility of miR-141 levels as a diagnostic tool and guide for better treatment selection.

When he's not occupied in the lab conducting research, Dr. Tewari is busy searching for new funding sources for the continuation of his work. And according to Dr. Tewari, this has not been an easy task for him and his team of researchers. He estimates that nearly two-thirds of his time is spent trying to acquire the financial resources needed to continue crucial research.

This struggle coincides with what recent statistics show. Since 2004, biomedical research costs have outpaced the growth in federal research funding. The result has been a decline of nearly $500 million in federal funding for cancer research.

"I apply to as many funding sources as possible," said Dr. Tewari. "Obtaining sustained funding for our research has proven extremely difficult."

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