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Pancreatic cancer is one of the deadliest cancers with a 5 year survival rate of <10% in the US. Ovarian cancer is less common, but it is the third most common reproductive-related cancer and the fifth most common cause of cancer-related deaths in women. Pancreatic cancer and aggressive ovarian cancers have too much KRAS signaling leading to more metastatic and progressive disease and poorer response to chemotherapies. This study focused on examining downregulation of KRAS, through stabilization of unique DNA structures, in SKOV3 pancreatic and CFPAC-1 pancreatic cancer cell lines using oligonucleotides and/or novel indoloquinoline compounds to downregulation KRAS. To date, the novel compound JM65 is the most promising compound that stabilizes the KRAS promoter structure, along with the oligonucleotides HpKRAS_G4 and HpKRAS_I1. Studies are ongoing to examine more compounds as well as to determine the effect of combining these approaches.



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Modulating KRAS Expression for Pancreatic and Ovarian Cancers