Drug Development Institute
Pelotonia Funds Are Advancing Development of Novel Anticancer Drugs
Working with the colleges of Medicine, Pharmacy and Business, the OSUCCC – James organized The Ohio State University (DDI) in 2011 to guide the development of promising anticancer drugs produced by OSUCCC – James researchers. Using external research-and-development service organizations, the DDI works with OSUCCC – James researchers to fast-track innovative compounds through the required FDA testing that is needed to proceed to clinical trials.
Timothy Wright, a former executive of several pharmaceutical companies, chairs the External Advisory Board for the Drug Development Institute. “The DDI focuses on solving important unmet needs in cancer and other diseases,” Wright says. “Our portfolio consists of novel mechanisms that address these unmet needs.” Bence Boelcskevy, PhD, also a former pharmaceutical executive, oversees the day-to-day operations. The DDI currently manages 15 drug-development projects. Seven are novel anticancer agents that receive Pelotonia support. Here are five examples of those.
PRMT5 is an enzyme that plays a vital role in cancer-cell growth. It 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 identified several unique drug candidates that inhibit PRMT5 activity. As part of a structured preclinical development program, further testing is being performed to confirm that these molecules stop tumor growth. The DDI is also facilitating a parallel project with these inhibitors in multiple sclerosis, an example of the institute’s expansion beyond oncology.
Tumor growth can be promoted or suppressed by signals that pass from one molecule to another in a cancer cell. STAT3 is an important molecule in some of these signaling pathways. OSUCCC – James researchers have synthesized a promising STAT3 inhibitor and are collaborating with Nationwide Children’s Hospital to define its effects in sarcoma. As part of a multi-pronged DDI research program they are also studying the effect of this inhibitor in melanoma, lung cancer, pancreatic cancer and oral cancer. Additionally, early evidence indicates that this molecule represses tumor growth in glioblastoma, a lethal form of brain cancer; in colon cancer, depending on tumor stage; and in ovarian and prostate cancer. Expansion of this program may be possible if these early results are confirmed.
RAS is a family of genes that make proteins involved in cell signaling pathways that regulate cell growth and cell death. Members of the RAS family include the genes KRAS, HRAS and NRAS. There is strong evidence that links mutations in these genes to cancer, and agents that block mutated RAS genes or their proteins may inhibit cancer growth. OSUCCC – James researchers have developed antibody-mimetic agents that inhibit the protein encoded by mutated KRAS. The mutant protein is 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 present in donated blood stem cells or a donated solid organ, it can cause post-transplant lymphoproliferative disease (PTLD) in transplant recipients, resulting in organ and transplant failure, that is often fatal. 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 an active ingredient 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, The Ohio State University, the University of Michigan and the pharmaceutical firm Venture Therapeutics have signed a co-development agreement and formed Sirona Therapeutics, a company to fully develop the Fenretinide oral patch. Development activities are in progress.