Leader: Dr. Katie Reindl
Project Title: Combination therapy: Targeting pancreatic cancer with an ROS inducer and gemcitabine
Mutations in the K-ras oncogene occur in more than 90% of Pancreatic Cancers (PC) where aberrant KRAS protein expression contributes to tumor progression, as well as resistance to chemotherapy and radiotherapy. Unfortunately, there are very few therapeutic strategies that are effective against cancers that are driven by K-ras mutations.
Recent studies have revealed that small-molecule inducers of oxidative stress can effectively kill both wild-type and K-ras mutant cancer cells. A promising new approach for treating PC cells derives, in part, from Dr. Reindl’s preliminary findings that illustrate how the small molecule, piperlongumine (PPLGM), induces cell death in PC cells through a reactive oxygen species (ROS)-dependent mechanism.
Furthermore, PPLGM synergizes with gemcitabine (GEM) to enhance toxicity to PC cells. Dr. Reindl’s group is focused on determining the mechanism of action and the therapeutic efficacy of PPLGM for PC, when combined with the currently used chemotherapy. Given that PC has nearly a 95 percent mortality rate, there is a critical need to identify potent compounds that could enhance the effectiveness of chemotherapies, especially with Kras mutant tumor cells that are often resistant to treatment.