A five-year, $1.8 million grant (R01CA203965) from the National Cancer Institute awarded to Rutgers Cancer Institute of New Jersey resident research member Wenwei Hu, PhD, will support research to further elucidate the mechanisms behind the most frequently mutated gene in human tumors - p53. The aim is to explore how chronic stress impacts cancer development, especially when cancers containing a mutation in p53, and identify molecular targets that would disrupt the effect of chronic stress on cancer development.
The p53 protein plays a central role in preventing cancer development, as loss of its tumor suppressor function has been shown to contribute greatly to cancer development. "Mutated p53 proteins often accumulate to high levels in tumors leading to increased activities that can increase tumor development. Preliminary data by our team suggest that chronic stress promotes this accumulation. Through our work, we aim to learn more about how mutated p53 proteins are stabilized in tumors in order to block the accumulation of mutated p53 in these tumors," notes Dr. Hu, who is part of Rutgers Cancer Institute's Genome Instability and Cancer Genetics Research Program. Hu and colleagues will utilize a well-established laboratory model that mimics chronic stress in humans to examine the regulation of p53 by chronic stress and neurohormones that are elevated during stressful periods.
"With more than 50 percent of all human tumors harboring p53 mutations, it is critical to identify the underlying molecular mechanism of this protein at the mutant form," adds Hu, who is an associate professor of radiation oncology at Rutgers Robert Wood Johnson Medical School. "In identifying molecular targets that impact stress signaling, there is an opportunity to develop novel therapies to treat those with mutated p53 cancers."