Micro molecules may mark cancer

Dr. Muneesh Tewari and colleagues find microRNAs regulating gene expression could lead to earlier detection of cancer
Dr. Muneesh Tewari (far right), Evan Kroh (center), Patrick Mitchell and Racheal Parkin
Dr. Muneesh Tewari (far right) described the discovery of microRNAs as a possible new class of biomarkers for early cancer detection "a real story of teamwork." Tewari said the project had many twists and turns, ups and downs, and credits research technicians Evan Kroh (center), Patrick Mitchell and Racheal Parkin for having the "perseverance and passion to make it happen." Photo by Carol Insalaco

Dr. Muneesh Tewari is the lead author of a study about the discovery of a possible new class of biomarkers for early cancer detection, microRNAs. Molecular workhorses that regulate gene expression, microRNAs are released by cancer cells and circulate in the blood, which gives them the potential to detect cancer at its earliest stages. Tewari and colleagues described their findings in the July 28 issue of the Proceedings of the National Academy of Sciences.

MicroRNAs, which act as brakes on different parts of a cell, keeping genes in check, have some advantages over protein-based early-detection systems, including that they can be detected potentially in smaller quantities and that the technology exists to rapidly develop microRNA-based early-detection tests, said Tewari, a scientist in the Human Biology and Clinical Research divisions. His work is focused on understanding why the brakes fail—allowing unchecked cell growth—in prostate and ovarian cancer.

“Current technology for developing tests to measure microRNAs in clinical samples is quite advanced, whereas the bottleneck for developing protein-based biomarkers is the slow process of generating assays for measuring specific proteins,” Tewari said.

The next steps are to identify specific microRNAs that can signal the presence of a variety of solid-tumor cancers at an early stage, and to further develop the technology to detect the microRNAs in minute quantities.

For the study, Tewari and colleagues, including research technicians Patrick Mitchell, Rachael Parkin and Evan Kroh, tested blood from mice and humans with advanced prostate cancers, as well as that from healthy controls. They measured microRNAs made by the tumors in both cases and controls, and they could distinguish which individuals had cancer based on blood microRNA measurement.

“This research shows that microRNAs, which weren’t previously thought of as markers of cancer in the blood, are a worthwhile class of molecules to study for the purpose of early cancer detection,” Tewari said.

MicroRNAs play a key role in a wide range of normal cell processes, including embryonic development and cell differentiation. The tiny regulatory molecules modulate the activity of specific messenger-RNA targets, which in turn give rise to proteins. Humans have 30,000 genes that can make messenger RNAs. There are more than 500 known microRNAs encoded by the human genome and each is thought to target up to hundreds of messenger RNAs.
That microRNAs existed in humans is in itself a recent discovery. Tewari’s group initially was studying their role in cancer development and maintenance because microRNAs are often dysregulated in cancer. During the course of those experiments, the scientists found that microRNAs circulate outside of cells and are remarkably stable.
“The results presented here establish the foundation and rationale to motivate future global investigations of microRNAs as circulating cancer biomarkers for a variety of common cancers,” the authors wrote.
In addition to those from the Hutchinson Center, scientists from the Institute for Systems Biology in Seattle, the Department of Urology at the University of Washington School of Medicine and the Department of Veterans Affairs Puget Sound Health Care System contributed to the research. The National Cancer Institute, the Pacific Ovarian Cancer Research Consortium Specialized Program of Research Excellence, the Pacific Northwest Prostate Specialized Program of Research Excellence, the Core Center of Excellence in Hematology and the Paul Allen Foundation for Medical Research funded the research.

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