The University of Houston College of Pharmacy is included in a $68.5 million funding package from the Cancer Prevention and Research Institute of Texas (CPRIT).
Ming Hu, Diana S-L. Chow Endowed Professor of Drug Discovery and Development, and Gregory Cuny, Joseph P. & Shirley Shipman Buckley Endowed Professor of Drug Discovery, received $1.4 million to fight familial adenomatous polyposis (FAP), a devastating and rare genetic disorder of the gastrointestinal tract that can cause hundreds or thousands of polyps inside the colon or rectum.
No effective treatment exists for FAP, which impacts 1-in-10,000 people, and unless the colon is surgically removed at an early age, 100% of patients will develop cancer.
There was once a glimmer of hope in the form of celecoxib, a selective COX-2 (cyclooxygenase 2) inhibitor, that was previously approved to treat FAP. COX-2 is an enzyme involved in the inflammation process. Unfortunately, its use for FAP was withdrawn because chronic use of celecoxib, which inhibits polyp growth, causes rare but serious cardiovascular toxicities including death.
Hu and Cuny are set to design new drugs to battle FAP, ones that will inhibit the activity of COX-2 in specific local areas of the body without affecting the entire body.
"We propose to develop locally bioavailable (i.e., no systemic exposure and toxicities) selective COX-2 inhibitors that are only available in the colon to suppress colonic COX-2 expression and reduce prostaglandin E2 levels, which is known to promote tumor growth," said Hu.
The locally bioavailable drugs will know exactly where to go in the body, designed to use the body's normal physiological processes to go straight to the areas of need.
They target the areas by being slowly metabolized in the colon but rapidly metabolized in the liver via a process called glucuronidation and undergoing recycling backed to the colon, minimizing systemic exposure. Our lead compound LBD-01 already has these properties, but its anti-COX-2 activity is lower than celecoxib. Hence, our research goal is to obtain more active compounds, while maintaining local bioavailability in the colon."
Gregory Cuny, Joseph P. & Shirley Shipman Buckley Endowed Professor of Drug Discovery
The project is co-led by three contributing investigators with complementary expertise: Noah Freeman Shroyer, Baylor College of Medicine; Dr. Eduardo Vilar Sanchez, a clinician who treats FAP patients at M.D. Anderson Cancer Center; and Rashim Singh, UH College of Pharmacy.
"Our project holds great promise for FAP patients by providing a new treatment paradigm that would be safe and effective," said Hu.
According to CPRIT, Texas leads the nation in its commitment to the war on cancer. Since 2010, CPRIT has funded 1,967 awards for cancer research, product development and prevention for a total amount of $3,542,257,795.
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