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'' S C O P E S M A G A Z II N E J U L Y 2 0 1 3 S C O P E S M A G A Z N E J U LY 2 0 12 A numbers game—new drug shows promise in blocking tumor growth Meet...Dr. Scott Coonrod There are hundreds of kinds of cancers, and although no two are exactly alike, at the core, they all have one weapon in common: fruitful cells that multiply out of control and are destined to overtake healthy cells. Dr. Scott Coonrod and his team at the College's Baker Institute for Animal Health are exploring new compounds that can shut down one of the main tools cancer cells use to turn on genes that cause rapid cell growth. His group is among the pioneers using cancer epigenetics to make discoveries like these. A relatively new field, cancer epigenetics investigates chemical changes in our genetic material and the proteins that regulate when and how a gene is turned on. Cancer epigenetics researchers have found that in tumorprone cells, certain modifications to small clusters of proteins in the cell's nucleosome appear to be stuck in the "on" position for genes involved in cell proliferation, leading to tumor growth and eventually metastasis. "One of our priorities is to find new drugs that block the activity of the enzymes that lead to these modifications and then test whether these new 'epigenetic inhibitor' drugs can block cancer growth," Dr. Coonrod, associate professor, said. Toward that goal, the Coonrod team has set its sights on an epigenetic enzyme nicknamed PADI2. The team's research confirmed the expression of this enzyme in the mammary gland and found that production of this enzyme is regulated by estrogen. They also found that PADI2 works in concert with estrogen to turn on proliferation genes by placing a new chemical, citrulline, at genes targeted by PADI2 and estrogen. Dr. Coonrod's team also made the very recent discovery that, in addition to es- trogen receptor-positive breast cancer (more than 75 percent of all breast cancers), PADI2 activity appears to be linked to other forms of breast cancer, including HER2-positive breast cancer, which accounts for about one of every five breast cancer cases. "We know that following removal of the primary tumor, many women take drugs such as Tamoxifen or Trastuzumab to prevent tumor recurrence," said Dr. Coonrod. "However, most women eventually become resistant to these drugs. Therefore, there is a critical need to develop new drugs that can block these cancer pathways. We believe that PADI2 may represent just such a drug, and we are currently trying to move this drug through the cancer drug development pipeline so that the inhibitors can be used to treat both human and companion animal cancers in the not-too-distant future." | 11