Massey scientists contribute to research involving the latest FDA-approved cancer therapies
VCU Massey Cancer Center doctors and scientists are making important discoveries involving cancer-fighting drugs recently approved by the U.S. Food and Drug Administration (FDA). Between August 2013 and July 2014, the FDA approved six new anticancer therapeutics, five of which target the unique molecular and genetic characteristics of an individual’s cancer. During this period, the FDA also approved new uses for five previously approved anticancer therapeutics, two new uses for imaging agents and one new use for a screening test.
The path from a drug or therapy’s initial discovery to FDA approval can take as long as ten years and is directly dependent on the results from research conducted by Massey and others within the biomedical community. Of every five to ten thousand compounds discovered to potentially play a role in a given disease, only about 0.01 to 0.1 percent become investigational new drugs that are submitted to the FDA for approval. Research – from observations to models to preclinical testing – is currently the best defense against cancer, and as a result, more people than ever are living longer after a cancer diagnosis. Below are a few highlights of research conducted by Massey doctors and scientists involving some of the newly approved anticancer therapeutics.
- Belinostat was granted accelerated approval by the FDA in July of 2014 for the treatment of patients with a certain type of non-Hodgkin lymphoma and works by targeting the unique genetic characteristics of an individual’s cancer. In 2012, based on his pre-clinical studies, Massey physician-scientist Steven Grant, M.D., received a $1.2 million “Grand Opportunities” grant from NCI to partially fund a now completed Phase 1 clinical trial for patients with acute forms of leukemia. The trial, led by Massey principal investigator Beata Holkova, M.D., used belinostat in combination with another novel targeted agent, bortezomib. Although results are still pending publication, the trial had two exceptional responders. Learn more
- Grant continues to conduct research on belinostat and is working to develop two clinical trials involving the drug for the treatment of lymphoma and acute myeloid leukemia (AML). Ibrutinib, a cell signaling inhibitor that works by preventing cancerous cells from responding to survival stimuli, was granted accelerated approval in November of 2013 for the treatment of patients with mantle cell lymphoma (MCL). In a pre-clinical study published in April of 2013, Grant discovered that a combination of ibrutinib and bortezomib could potentially be an effective new therapy for several forms of blood cancer, including diffuse large B-cell lymphoma (DLBCL) and MCL. Learn more
- Sorafenib, a multikinase inhibitor that works by slowing the spread of cancer cells, was approved by the FDA in November of 2013 for the treatment of a certain type of thyroid cancer. It was previously approved in 2005 for the treatment of kidney cancer and liver cancer. In 2012, Grant found another use for the drug—he published a pre-clinical study in which he discovered that sorafenib usedin combination with the targeted agent, obatoclax, kill AML cells much more effectively than when the drugs are administered individually. Learn more
- In July of 2013, Massey scientist Paul Dent, Ph.D., published a pre-clinical study that demonstrated that the drugs sorafenib and regorafenib synergize with a class of drugs known as PI3K/AKT inhibitors to kill a variety of cancers, including colon, liver, lung, kidney, breast and brain cancer cells, while having little effect on noncancerous cells. Learn more
- In a pre-clinical study published in 2010, Dent and Massey scientist Paul B. Fisher, M.Ph., Ph.D., developed a novel virus-based gene therapy for renal cell carcinoma that has been shown to kill cancer cells not only at the primary tumor site but also in distant tumors not directly infected by the virus. The therapy involves sorafenib. Learn more
- Massey physician and principal investigator, Andrew Poklepovic, M.D., led a now completed Phase 1 clinical trial to study the use of sorafenib in combination with pemetrexed (a multitargeted antifolate that was co-developed by Massey scientist Richard Moran, Ph.D., and prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells) to treat advanced malignancies. The trial’s concept is based on the collaborative laboratory work of Massey scientists Dent and Moran, who together discovered that the combination of sorafenib and pemetrexed leads to toxic autophagy, a form of cancer cell death. Results of the trial are still pending publication, however the trial saw very good responses in breast cancer, including triple negative breast cancer—a disease that is very difficult to treat. Learn more
Grant is a hematologist-oncologist, the Shirley Carter Olsson and Sture Gordon Olsson Chair in Oncology Research, associate director for translational research, co-leader and member of the Developmental Therapeutics program and member of the Cancer Cell Signaling program at Massey.
Poklepovic is a medical oncologist and member of the Developmental Therapeutics research program at Massey as well as assistant professor in the Division of Hematology, Oncology and Palliative Care at VCU School of Medicine.
Dent is the Universal Corporation Chair for Cancer Cell Signaling and member of the Developmental Therapeutics research program at Massey as well as vice chair of the Department of Neurosurgery at VCU School of Medicine.
Fisher is the Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at Massey, professor and chair of the Department of Human and Molecular Genetics at the VCU School of Medicine and director of the VCU Institute of Molecular Medicine (VIMM).
Moran is the Paul M. Corman, M.D., Chair in Cancer Research, associate director for basic research and co-leader and member of the Developmental Therapeutics research program at Massey as well as professor of pharmacology and toxicology at the VCU School of Medicine.