Drug Development Institute & Pelotonia: Advancing Development of Novel Anticancer Drugs
The Ohio State University Drug Development Institute (DDI) was founded in 2011 to guide the development of promising anticancer drugs produced by OSUCCC – James researchers. The DDI aims to fast-track innovative compounds through the FDA testing that must come before a possible clinical trial. Timothy Wright, former executive of several pharmaceutical companies, chairs the External Advisory Board for the DDI. “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.
Among the current Pelotonia supported projects are the development of STAT3, PRMT5 and RAS inhibitors. STAT3, PRMT5 and RAS are molecules that play vital roles in cancer-cell growth.
PRMT5, for example, is highly expressed in lymphoma, acute leukemia and other hematologic malignancies, and in solid tumors. 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.
Similarly, OSUCCC – James researchers have synthesized a promising STAT3 inhibitor and are collaborating with Nationwide Children’s Hospital to define its effects in sarcoma. 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. 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.
Research on RAS is well on its way as well. RAS is a family of genes that make proteins involved in regulating cell growth and cell death. Members of the RAS family include the genes KRAS, HRAS and NRAS. Mutations in these genes are strongly linked to cancer, and agents that block mutated RAS genes, or their proteins, might 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.
In addition to work on molecular inhibitors, the DDI manages research on the 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 in a donated 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.
The development of a Fenretinide oral patch is also managed by the DDI. 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 that will fully develop the Fenretinide oral patch. Development activities are in progress.