Two Mount Sinai School of Medicine researchers are among a select group of scientists from around the world who have been recognized by the National Cancer Institute (NCI) for their quest to answer the most pressing questions about cancer. Stuart Aaronson, MD, Professor and Chair of Oncological Sciences and Ross Cagan, PhD, Professor of Oncological Sciences at Mount Sinai, have received the NCI's new "Provocative Questions" grant, which was established to explore the important yet less obvious questions about cancer that may have been neglected in this era of significant discovery.
Provocative Question: Why do many cancer cells die when suddenly deprived of a protein encoded by an oncogene?
The grant will support Dr. Aaronson's research on signaling pathways responsible for a little-understood phenomenon called oncogene addiction. Oncogenes are mutant genes that scientists believe are key to tumor survival and progression. Disruption of the signaling pathway in these oncogenes has been shown to halt tumor growth or lead to tumor cell death. Dr. Aaronson's lab is exploring the signaling activity of one such pathway called Wnt, which plays a key role in regulating self-renewal of a variety of embryonic and adult stem cells and is a starting point for tumor development.
Dr. Aaronson's lab has found that inhibition of activated Wnt signaling can block growth and complement the effects of chemotherapy and radiation, leading to tumor cell death. The goals of this grant are to investigate the signaling pathways responsible for Wnt oncogene addiction, and discover its molecular basis.
"While increasing efforts are being made to develop effective inhibitors of Wnt signaling in tumors, to date, few, if any, have entered into clinical development," said Dr. Aaronson. "Our NCI grant will support our research to identify and characterize specific and potent Wnt-targeted drugs that can disrupt this oncogene addiction in tumor cells and increase the efficacy of therapy for Wnt-activated human cancers. We are honored to be recognized by the NCI for our efforts in this area."
Provocative Question: How does obesity contribute to cancer risk?
Research has shown a distinct connection between obesity and cancer risk, but the mechanism behind that risk is unclear. With support from the NCI grant, Dr. Cagan's laboratory will create a model of pancreatic cancer in fruit flies to learn the molecular signatures that predict how a tumor responds to diet-induced obesity. Dr. Cagan's team will also perform a genetic screen on fruit flies to learn which genes promote tumor growth. Armed with this information, Dr. Cagan's team will test a variety of drugs approved by the U.S. Food and Drug Administration to determine which ones may prevent diet-related tumor growth.
"The fact that high-sugar diets cause tumors to become more aggressive is long-established, but we still do not know why," said Dr. Cagan. "This NCI grant will allow us to better explore the pathways that link obesity to enhanced tumor growth and to explore whether compounds that address this link are potentially useful as treatments. We appreciate the opportunity to take a non-traditional approach to an old question."
The Provocative Questions grant will support the research of Drs. Aaronson and Cagan for five years. They will each receive $351,713 in the first year. Allocations for subsequent years are to be determined.
The Provocative Questions program seeks to identify and solve perplexing problems facing cancer research. It is intended to build on specific advances in the understanding of cancer and cancer control; address broad issues in the biology of cancer that have proven difficult to resolve; take into consideration the likelihood of progress in the foreseeable future; and address ways to overcome obstacles to achieving long-term goals. Out of 750 applications, only 24 were awarded. For more information, please visit http://provocativequestions.nci.nih.gov/.
The Mount Sinai Medical Center