Pancreatic cancer is one of the most lethal carcinomas in the U.S., estimated to kill over 43,000 people in 2017 alone. Compared to other cancers, it is exceptionally aggressive with a 5-year survival rate of 8.2%. Breast cancer, although more prevalent, has a 5-year survival rate of 89.7%. The lack of effective early detection and a resistance towards conventional chemotherapies both contribute to the lethality of this disease. Currently, the most common chemotherapies used clinically are Gemcitabine and 5-Fluorouracil, which only extend life by about a year. Therefore, there is an acute need for new pancreatic cancer treatments. In 2006, Awale et. al. isolated the naturally occurring compound angelmarin from the root of the Japanese medicinal plant Angelica pubescens. They found that it exhibited 100% preferential cytotoxicity against PANC-1 cancer cells only when under nutrient-deprived conditions. As pancreatic cancer cells are intrinsically under nutrient-poor conditions, this specificity is promising. Based on the core structure of angelmarin, our research group synthesized several structural analogs of the natural product. Through several structure-activity relationship (SAR) studies our lab arrived at our current lead compound, DCM-MJ-I-21. In vitro antiproliferative cell assays showed that this compound is both highly selective and potent, enabling it to kill 100% of PANC-1 cells under nutrient-deprived conditions at low micromolar concentrations. Comparison studies in both 2D and 3D cell cultures comparing DCM-MJ-I-21 against gemcitabine, 5-fluorouracil, and etoposide demonstrated our compound’s superior potency as well as selectivity under nutrient-deprived conditions. Preliminary studies on a combination therapy incorporating DCM-MJ-I-21 and etoposide (VP-16) show improved efficacy over DCM-MJ-I-21 alone. We therefore have a novel anti-pancreatic cancer agent that shows promise both as a monotherapy and combination therapy.

Promising anti-pancreatic cancer compound: Investigations into combination therapies and stability of DCM-MJ-I-21 in vehicle

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.