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Pancreatic cancer is the third leading cause of cancer-related deaths, with a 1-year survival rate of 29% and a 5-year survival rate of 7%. Pancreatic cancer often goes undiagnosed until its late stages, at which point treatment options become limited to chemotherapy and radiation therapy, which are often ineffective at substantially prolonging life. Thus, there is a pressing need for improved pharmacologic treatment for pancreatic cancer. DCM-MJ-I-21, a compound developed in our laboratory, exhibits cytotoxicity against the human pancreatic cancer cell line PANC-1, with preferential cytotoxicity under nutrient deprived conditions, which mimic the tumor microenvironment. This study investigated the mechanism of action of DCM-MJ-I-21. Data revealed DCM-MJ-I-21 inhibits one or more late-stage steps of the autophagy pathway in PANC-1 cells. This study also explored the effects of DCM-MJ-I-21 as an agent in combination chemotherapy with etoposide, a topoisomerase II inhibitor. Results revealed that these compounds synergize in PANC-1 cells, with differing dose and time effects following 24 versus 48 hours of treatment. Future research ought to explore the effects of combination chemotherapy at more frequent time points in order to fine-tune dosage and timing data. Data should also be evaluated in PANC-1 spheroid assays to determine whether two-dimensional data recapitulates in three-dimensional conditions.
Available for download on Tuesday, April 19, 2022