Targeting Cytoplasmic Tyrosine Kinases in Cancer: : The Paradigm of Bcr-Abl in Chronic Myeloid Leukemia.DE

Protein kinases are critical regulators of cell signaling and represent one of the most successful classes of drug targets in oncology. Among them, cytoplasmic tyrosine kinases (CTKs) play a pivotal role in controlling cell growth, survival, and differentiation. This review provides a comprehensive overview of CTKs as therapeutic targets, with a particular focus on the c-Abl kinase and its oncogenic counterpart, Bcr-Abl, in Chronic Myeloid Leukemia (CML). A significant portion of the review is dedicated to the development and clinical evolution of Bcr-Abl inhibitors, from first-generation ATP-competitive drugs like imatinib to second- and third-generation agents designed to overcome resistance. Finally, we discuss the clinical landscape of kinase inhibitors and future perspectives, positioning the Bcr-Abl story as a paradigm for targeted cancer therapy.