Work

Extreme mutational selectivity of axitinib limits its potential use as a targeted therapeutic for BCR-ABL1-positive leukemia

Year: 2015

Type: article

Abstract: Clinical use of the BCR-ABL1 selective tyrosine kinase inhibitor (TKI) imatinib has markedly improved the prognosis of chronic myeloid leukemia (CML). Next-generation TKIs, including nilotinib, dasatinib, bosutinib and ponatinib, effectively control resistance due to BCR-ABL1 point mutations. Ponatinib, the only US Food and Drug Administration (FDA)-approved TKI with activity against the clinically prevalent BCR-ABL1 T315I mutant, 1 has been linked to severe vascular occlusive events 2 , 3 , 4 , 5 , 6 at a dose of 45 mg once daily, and lower doses are being explored (clinicaltrials.gov identifier NCT02467270). Emergence of BCR-ABL1 compound mutations can confer high-level resistance to all available TKIs, including ponatinib, indicating a need for new therapeutic options. 7

Source: Leukemia

DOI: 10.1038/leu.2015.318