New Molecular-Targeting Therapy for Chronic Myeloid Leukemia

―The Clinical Application of Allosteric Regulation―

Abstract

The outcome of patients with chronic myeloid leukemia (CML) has dramatically improved with tyrosine kinaseinhibitors (TKIs). Five TKIs, imatinib, nilotinib, dasatinib, bosutinib, and ponatinib, are currently available inJapan. However, some patients still respond insufficiently to TKI. Additionally, adverse events that cause TKIintolerance are a critical concern. In Japan and the United States, asciminib, a CML therapeutic drug with a newmechanism of action, has become available in the daily clinic. This article outlines the unique mechanism ofaction of this new drug. Asciminib targets the allosteric regulation of the BCR-ABL1 oncoprotein, a substantialdriver of CML development. In addition, the latest clinical trials that led asciminib to its clinical application aredescribed here.