Darren R. Carpizo
Robert Wood Johnson Medical School
Department of Surgery
The Cancer Institute of NJ
195 Little Albany Street
New Brunswick, NJ 08901
Pancreatic Cancer, Liver Cancer, Metastatic Colorectal Cancer, Biliary Cancers, Whipple Surgery, Radioembolization of Liver Tumors, Regional Liver Chemotherapy, P53 Targeted Drug Development, Hedgehog Signaling in Pancreas Cancer, P53 Tumor Biology, and Mouse models of Pancreas Cancer
Recurrence of patients' cancers following surgery for gastrointestinal cancers is one of the most significant clinical problems facing surgical oncologists today. Unfortunately recurrence is a problem that can only be remedied by more effective chemotherapy. Therefore, the focus of my laboratory research is in Developmental Therapeutics (novel anti-cancer drugs). Pancreas cancer is a disease that is not only very aggressive, but also the chemotherapy is only marginally effective. I am leading a translational clinical trial to study a novel class of drugs called Hedgehog inhibitors in patients with surgically resectable pancreas cancer so that we may understand more completely how these exciting drugs work in humans.
The next generation of anticancer drugs is defined by compounds that selectively kill cancer cells while leaving normal cells undisturbed. My colleagues at CINJ and I have identified a compound targeting one of the most commonly mutated genes in human cancer, TP53. TP53 is second only to K-Ras as the most commonly mutated gene in pancreatic cancer with point mutations occurring in 75 percent of patients. Considered a tumor suppressor, the protein p53's normal function is to tightly regulate cellular growth and division, making sure that cells only divide in the appropriate time and place. However, upon mutation, p53 loses its function and allows uncontrolled proliferation of cells, a hallmark of tumor formation. This compound selectively kills cancer cells with one of the most commonly found p53 mis-sense mutants, p53-R175H, by restoring the normal structure and function to this mutant p53 protein. This work was recently published in the journal Cancer Cell (2012) and I have received a grant from the Pancreatic Cancer Action Network to further examine the functions of p53.