Novel aspects of therapy with the dual Src and Abl kinase inhibitor bosutinib in chronic myeloid leukemia

Abstract

The dual Src/Abl kinase inhibitor bosutinib (SKI-606) targets the tyrosine kinase brc-abl, the key enzyme in the development of chronic myeloid leukemia (CML). In clinical trials, bosutinib yielded promising results with regard to efficacy, tolerability and toxicity in first-, second- and third-line therapy of CML patients. Remarkably, bosutinib is able to overcome most imatinib-resistant BCR-ABL1-1 mutations except V299L and T315I. Mostly, low-to-moderate grade gastrointestinal toxicitis are the most common treatment-emergent adverse events observed under bosutinib. Unlike other tyrosine kinase inhibitors approved for CML treatment to date, bosutinib shows only minimal inhibitory activity against c-KIT and the PDGF receptor. This may be causative for its favorable hematologic toxicity profile. In this review, the authors give an overview on the mechanism of action and currently available preclinical and clinical data for bosutinib in CML.

Keywords::

• BCR-ABL-1
• bosutinib
• chronic myeloid leukemia
• dasatinib
• imatinib
• nilotinib
• point mutation
• SRC
• SRC/ABL kinase inhibitor
• tyrosine kinase

Financial & competing interests disclosure

T Brümmendorf has received honoraria for satellite symposia oral presentations from Pfizer and acts as a consultant on the scientific advisory board of Pfizer, Novartis and Bristol-Myers Squibb. T Brümmendorf holds a patent on the use of imatinib and hypusination inhibitors. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.