title: Ponatinib for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia.
abstract: Ponatinib is a novel, next-generation, small-molecule tyrosine kinase inhibitor with potent activity against the BCR-ABL fusion oncogene as well as all other ABL kinase domain mutations that confer resistance to earlier generation tyrosine kinase inhibitors. Due to its unique structure, it is the only tyrosine kinase inhibitor with the capability to counter the highly resistant T315I or gate-keeper mutation in leukemic cells that express the Philadelphia chromosome. This review will focus on the preclinical pharmacology, pharmacokinetics and clinical utility of ponatinib in the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive adult acute lymphoblastic leukemia.
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: V
authors.initials: V
authors.lastname: Narayanan
authors.forename: D A
authors.initials: DA
authors.lastname: Pollyea
authors.forename: J A
authors.initials: JA
authors.lastname: Gutman
authors.forename: A
authors.initials: A
authors.lastname: Jimeno
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011724:Pyridazines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; C545373:ponatinib; D011505:Protein-Tyrosine Kinases
keywords: Acute lymphoblastic leukemia; Chronic myeloid leukemia; Ponatinib; T315I mutation; Tyrosine kinase inhibitor