Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib
Drug Resistance, Neoplasm
Leukemia, Lymphocytic, Chronic, B-Cell
Phospholipase C gamma
Resistance to the irreversible BTK inhibitor ibrutinib often involves mutation of a cysteine residue where ibrutinib binding occurs. This finding, combined with two additional mutations in PLCγ2 that are immediately downstream of BTK, underscores the importance of the B-cell-receptor pathway in the mechanism of action of ibrutinib in CLL. (Funded by the National Cancer Institute and others.).