OSU Drug Development Institute (DDI)
Pelotonia Funds Support Development of Anticancer Agents by OSU Researchers
In 2011, the OSUCCC – James collaborated with the colleges of Medicine, Pharmacy and Business in organizing The Ohio State University Drug Development Institute (DDI) to guide the development of promising anticancer drugs produced by OSUCCC – James researchers.
Timothy Wright, a former executive of several pharmaceutical companies, directs the institute in conjunction with Bence Boelcskevy, PhD, also a former pharmaceutical executive. They are fast-tracking promising compounds through the testing needed for use in clinical trials.
“The DDI is focused on solving important unmet needs in cancer and other diseases,” Wright says. “Our portfolio consists of novel mechanisms to address these unmet needs.” Currently, the institute is facilitating 15 projects involving seven novel anticancer agents within five areas of study that are supported by Pelotonia dollars:
PRMT5, an enzyme that plays a vital role in cancer-cell growth, is highly expressed in lymphoma, acute leukemia and other hematologic malignancies, and in solid tumors, including head and neck, lung, melanoma and brain. OSUCCC – James researchers have developed a firstin-class PRMT5 inhibitor that they believe will stop tumor growth. The inhibitor is in preclinical testing. The DDI is also facilitating a parallel project with this inhibitor in multiple sclerosis, so the institute’s influence is expanding beyond oncology.
Tumor growth can be promoted or suppressed by signaling pathways in cancer cells, including STAT3. The tumorsuppressor role of STAT3 has been reported in human glioblastoma (brain cancer). Recent studies have shown that STAT3 also has an inhibiting role in colon cancer, depending on tumor stage. OSUCCC – James researchers are collaborating with Nationwide Children’s Hospital to define the STAT3 effects in sarcoma, and they are initiating a multi-pronged research program to study the effects of this inhibitor in melanoma, lung, pancreatic, breast and prostate cancer.
The National Cancer Institute (NCI) defines RAS as a family of genes that make proteins involved in cell signaling pathways, cell growth and cell death; members of the RAS family include KRAS, HRAS and NRAS. The NCI says these genes may cause cancer when they are mutated, but agents that block mutated RAS genes or their proteins may inhibit cancer growth. OSUCCC – James researchers have developed antibody-like agents that can inhibit KRAS, a protein implicated in 30 percent of all cancers.
Epstein-Barr Virus Vaccine
Epstein-Barr virus (EBV) is a common infection that causes mononucleosis. It is also associated with Hodgkin’s lymphoma, Burkitt’s lymphoma and other cancers; with conditions associated with HIV infection; and with autoimmune diseases. If EBV is in a blood stem cell or a donated solid organ, it can cause post-transplant lymphoproliferative disease (PTLD). This often-fatal complication can follow a stem-cell or organ transplant. Researchers at the OSUCCC – James are developing an EBV vaccine to prevent PTLD and help other EBV-related conditions.
Fenretinide Oral Patch (a Pharma Industry Partnership)
About 300,000 Americans annually develop precancerous lesions in the mouth that can progress to oral cancer, and nearly 36,000 people in the United States develop oral cancer yearly. These lesions are removed surgically, but they tend to recur. A team of OSUCCC – James researchers has developed a patch that adheres to the lesions and releases a promising anticancer drug called fenretinide to treat them. The patch could provide an alternative to surgery and reduce the incidence of oral cancer. With help from the DDI, Ohio State and a pharmaceutical firm called Venture Therapeutics have signed a co-development agreement and formed a company, Serona Therapeutics, that is incorporated to fully develop the fenretinide oral patch. Preclinical work is complete. An Institutional New Drug (IND) filing with the NCI and the start of clinical trials are projected for 2015.