Abstract: This research project identifies previously unknown vulnerabilities in pancreatic cancer cells that can be used to target cancer treatment. It involves the manipulation of a step in the central dogma process (the biological process by which genes are expressed to synthesize proteins). The function of an essential protein (spliceosome) is inhibited by treatment by splicing inhibitors biflavonoid-isoginkgetin and pladienolide-B. This caused pancreatic cancer cells to express versions of genes (isoforms) that weaken the cells by inhibiting splicing (an essential process that aids in the synthesis of final mRNA). These newly discovered weaknesses, cancer-specific differential isoform expressions, are places to target for treatment. Splicing was inhibited using two inhibitors: pladienolide-B and biflavonoid-isoginkgetin. Three concentrations of each inhibitor were applied on four different cell types: aggressive and less aggressive pancreatic cancer cells (test), and healthy pancreatic and kidney cells (control and general control). The expression of eight different genes and their isoforms were tested across all cell lines using reverse transcription polymerase chain reaction. This resulted in 256 isoform expression data points. These results identified three gene-specific weaknesses and missing defense mechanisms in the cancer cells. The fact that these vulnerabilities were specific to cancer cells led to the belief that splicing has a different mechanism in cancer cells than healthy cells. Hence, the levels of the DBR1 protein (clean-up protein in the splicing process) were tested in all four cell types using Western Blotting (Figure 1). These results (lower DBR1 expression in cancer cells) provided further evidence of a different splicing mechanism in cancer cells. Future research should investigate the splicing mechanism in pancreatic cancer cells, seek a molecular basis for the absence of the DBR1 protein, and use the newly discovered vulnerabilities for treatment development.