Researchers in the lab of Jen Jen Yeh, MD, have identified two kinotypes in pancreatic cancer that differentiate the two established molecular subtypes of pancreatic ductal adenocarcinoma (PDAC), as reported in a paper recently published in Cancer Discovery.
Laura Peng, PhD, Yi Xu, PhD, and their coauthors uncovered three kinome subgroups that make up two dominant tumor-intrinsic kinome subtypes called kinotypes. A kinome is a complete set of kinases, which are proteins that help control signals and processes in cells. Kinases work by attaching phosphate groups to other molecules, helping to regulate functions like growth, energy use, and cell communication.
The kinotypes discovered by Peng and Xu demonstrate enrichment of different kinase classes and help explain the biological differences in now well-known subtypes of PDAC—basal-like and classical.
Most notably, the kinotype characterizing basal-like tumors shows enrichment of receptor tyrosine kinases including EGFR, whereas the kinotype characterizing classical tumors is enriched in the understudied kinases involved in Wnt signaling and immune pathways.
Their findings, which were validated in two clinical trials, demonstrate that only patients with basal-like kinotype tumors—widely shown to resist chemotherapy—derive significant benefit from EGFR inhibitors. These results map out a comprehensive tumor-intrinsic kinome landscape of PDAC that strongly supports actionable kinotype-specific kinase targets and provides a roadmap for the use of kinase inhibitors in the treatment of PDAC.
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—Tyler Rice, UNC Lineberger Pancreatic Cancer Center of Excellence