KIT V560D

We describe the clinical course and the outcome with the use of avapritinib, midostaurin, and decitabine-cedazuridine. Trial Registration: ClinicalTrials.gov identifier: NCT00782067.

We found that farnesyltransferase inhibitors tipifarnib and lonafarnib, which inhibit RAS activity, inhibited ERK activation mediated by both wild-type and KIT mutants, which often occur in gastrointestinal stromal tumors. Similar to the primary KIT mutations, secondary mutations of KIT-induced ERK activation and cell response were inhibited by both inhibitors. Our results suggested the potential benefit of farnesyltransferase inhibitors either alone or combined with imatinib in the treatment of gastrointestinal stromal tumors carrying KIT mutations.

Currently, sunitinib is the only receptor tyrosine kinase inhibitor approved for TC treatment... Our findings provide an enhanced road map for the etiology of TC. Further investigation is warranted into the roles of NF-κB pathway and epigenetic regulators dysfunction in TC pathogenesis and their potential for clinical trials.

Conclusion In BaF3 cells, PI3Kδ subtype plays a major role in KIT activation and its downstream signal transduction, while in GIST-T1 cells, PI3Kβ subtype plays a major role in KIT activation and its downstream signal transduction. These results indicate that PI3K isoforms play different roles in KIT mutation-mediated cell transformation depending on the host cells.