(ChemotherapyAdvisor)– The pancreatic protein, PEAK1, is a novel biomarker and new therapeutictarget in pancreatic ductal adenocarcinoma (PDAC), according to researchers ofthe University of California at San Diego and their colleagues. This conclusionis based on a paper entitled “KRas Induces a Src/PEAK1/ErbB2 KinaseAmplification Loop That Drives Metastatic Growth and Therapy Resistance inPancreatic Cancer,” which was published in CancerResearch on May 15. In this study, the investigators aimed to establish theearly biomarkers and effective therapeutic strategies so desperately needed totreat PDAC, a disease with a dismal 5-year survival rate.

Inthis study, human biopsies of PDACs and pancreaticintraepithelial neoplasia contained higher than normal expression levels of thenovel tyrosine kinase PEAK1. Thepresence of an oncogenic KRas gene also induced a PEAK1-dependent kinase amplification loopbetween Src, PEAK1, and ErbB2 to drivePDAC tumor growth and metastasis in vivo. The investigator alsodiscovered that inhibiting ErbB2 expression increased PEAK1 expression and tumor growth invivo; this finding suggested a rationale for the common therapeuticresistance found in PDACs. “Importantly, PEAK1inactivation sensitized PDAC cells to trastuzumab and gemcitabine therapy,” theinvestigators wrote.


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Theinvestigators concluded that “PEAK1 isa novel biomarker, critical signaling hub, and new therapeutic target in PDACs.”

Abstract