Abstract
Pancreatic cancer (PC) is the fourth leading cause of cancer deaths and often develops without early symptoms. The abysmal 5‐year overall survival rate of only 6% has fueled the search for novel biomarkers and drug targets. Mutations in K‐ras are involved in >;90% of PC and enzymes that target ras metabolism have been explored as anticancer drug targets. The polyisoprenylation pathway (PP) is essential for proper ras function. Inhibition of polyisoprenylated methylated protein methyl esterase (PMPMEase) induces the apoptosis of various cancer cells. Immunohistochemical analysis of a PC microarray revealed overexpression of PMPMEase compared to controls. Mean PMPMEase staining intensity for pancreatic ductal adenocarcinoma (393.6±14.4) was statistically greater than normal (115.0±7.6, p<0.0001) and normal adjacent tissues (145.0±8.6, p<0.0001). Polyisoprenylated cysteinyl amide inhibitors (PCAIs) designed as potential anticancer drugs showed micromolar Ki values against PMPMEase. Taken together, PMPMEase may serve as a novel biomarker and drug target in the management of pancreatic cancer.
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