Article Abstract

A new promising quinazoline-derived Pan-KIT mutant inhibitor for the gastrointestinal stromal tumors (GIST) management

Authors: Nathália C. Campanella, Viviane A. O. Silva, Rui Manuel Reis


Gastrointestinalstromal tumors (GISTs) are the most common mesenchymal tumors commonly locatedin stomach (60%) and small intestine (25%), but they can also be found in otherparts of the gastrointestinal tract (1). GISTs are characterized by hotspotmutations in KIT and PDGFRA oncogenes. These oncogenes codifytype III receptor tyrosine kinase which, after binding to the ligand [stem cellfactor (SCF) and platelet-derived growth factor (PDGF), respectively], resultsin receptor homodimerization and kinase activation (2,3). The presence ofactivating mutations of KIT and PDGFRA causes ligand-independentkinase and downstream signaling pathways activation, including MAPK, PI3k/AKT,and STAT3 pathways (1,4).