GRANTEE: Channing Der, PhD
University of North Carolina
Co-Principal Investigator: Jason Fleming, MD, MD Anderson Cancer Center
Co-Principal Investigator: Krister Wennerberg, PhD, University of Helsinki, Finland
Research Project: Defining novel combination KRAS-targeted therapeutic strategies
Award: 2015 Pancreatic Cancer Action Network – AACR Research Acceleration Network Grant
Award Period: July 1, 2015 – June 30, 2018
Dr. Der is the Sarah Graham Kenan Professor of Pharmacology at the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill. He received his PhD from the University of California at Irvine and completed his postdoctoral studies at the Dana-Farber Cancer Institute and Harvard Medical School. In 2012, Dr. Der was awarded an Innovative Grant from the Pancreatic Cancer Action Network, funded by Tempur-Pedic® Retailers.
Dr. Fleming is a pancreatic surgeon at MD Anderson and serves as director of the tissue acquisition and biorepository core for the Pancreas Cancer Research Program at MD Anderson. Dr. Fleming initiated and developed the first direct xenograft program in gastrointestinal cancer at MD Anderson. Dr. Fleming earned his BS at Vanderbilt University, MD at University of Tennessee, and underwent his medical training at UT Southwestern Medical Center, Hamon Center for Therapeutic Oncology and MD Anderson Cancer Center. Dr. Fleming is a member of the Pancreatic Cancer Action Network’s Scientific and Medical Advisory Board.
Dr. Wennerberg is the FIMM-EMBL Group Leader at the Institute for Molecular Medicine Finland in Helsinki, Finland. He earned his BS and PhD degrees at Uppsala University in Uppsala, Sweden. He underwent his postdoctoral training at the University of North Carolina at Chapel Hill. Dr. Wennerberg’s role in this project will be to lead the drug sensitivity profiling work.
The most common genetic alteration in pancreatic tumors is mutation of the gene KRAS. While blocking the expression or activity of mutant KRAS protein would be an attractive strategy to stop the growth of pancreatic tumors, efforts to inhibit KRAS have been ineffective to date. Instead, there are treatment strategies that include blocking the different protein pathways that become activated by KRAS. However, challenges include toxicity to normal cells leading to side effects, ineffectiveness of the drugs currently available to block these pathways, and ability of the cancer cells to become resistant to these types of drugs. Drs. Der, Fleming and Wennerberg therefore propose to identify novel combinations of drugs to attack both of the most significant protein signaling pathways activated by KRAS. Their drug screening effort will apply the largest collection of chemical inhibitors ever assembled for anti-cancer drug testing against pancreatic cancer. They will also scrutinize the mechanisms by which the cancer cells may become resistant to these inhibitors, in order to circumvent the resistance and effectively treat the tumor.