Examination of Drug Compound on Common Cancer Mutation
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A $250,000 grant awarded to Rutgers Cancer Institute of New Jersey surgical oncologist Darren R. Carpizo, MD, PhD, will further aid the work of the physician-scientist in exploration of mechanisms behind the p53 gene – which is the most commonly mutated gene in human cancer. The funding from the Breast Cancer Research Foundation will help Dr. Carpizo build upon previous research from his laboratory examining a drug compound that restores tumor suppressor function of p53, with an aim of providing a foundation for the development of a new type of anti-cancer drug.
Known as the “guardian of the human genome,” the p53 gene recognizes cellular stress and stops cell proliferation by either allowing the cell to recover from the stress or activating a protein that induces a program to kill the cell if the damage can’t be repaired. The loss of this function can result in cancer cells escaping a controlled environment and multiplying throughout the body. Previous research by Carpizo’s laboratory identified a drug compound that restores this tumor suppressor function by targeting a common p53 mutation. Along with restoring structure and function to the p53 mutant protein, this drug compound has the ability to to activate a program that selectively kills cancer cells with this particular mutation while leaving normal cells undisturbed. The mechanism behind this action is characterized as a “zinc metallochaperone” and is considered novel.
This latest grant will fund research to determine the application of zinc metallochaperones in breast cancer. One form of breast cancer called “triple negative” breast cancer is known for its biological aggressiveness and lack of effective chemotherapy options. The preliminary data that Carpizo and colleagues have generated suggest that zinc metallochaperones have activity and that breast cancers with a mutation in the BRCA1 gene are particularly sensitive to zinc metallochaperones. These ideas will be explored further in this grant.
“Restoring the tumor suppressor ability of p53 with a drug is paramount in anti-cancer drug development,” notes Carpizo, who is an associate professor of surgery and pharmacology at Rutgers Robert Wood Johnson Medical School. “By further examining zinc metallochaperones on other p53 mutants that are similarly structured, we have an opportunity to increase the potential pool of patients that could theoretically benefit from zinc metallochaperones resulting in broad activity against all cancer types. I am grateful to the Breast Cancer Research Foundation for its support of this work.”
The laboratories of Stewart Loh, PhD, at SUNY Upstate Medical University and Rutgers Cancer Institute Associate Member David Augeri, PhD, from Rutgers Translational Sciences at Rutgers University are collaborating on the work. The project period runs for one year.