Ponatinib: a novel multi-tyrosine kinase inhibitor against human malignancies

Abstract

Fiona H Tan,1,2 Tracy L Putoczki,1,3,4 Stanley S Stylli,1,5 Rodney B Luwor1 1Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia; 2Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; 3Inflammation Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; 4Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia; 5Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia Abstract: Human malignancies are often the result of overexpressed and constitutively active receptor and non-receptor tyrosine kinases, which ultimately lead to the mediation of key tumor-driven pathways. Several tyrosine kinases (ie, EGFR, FGFR, PDGFR, VEGFR), are aberrantly activated in most common tumors, including leukemia, glioblastoma, gastrointestinal stromal tumors, non-small-cell lung cancer, and head and neck cancers. Iclusig™ (ponatinib, previously known as AP24534) is an orally active multi-tyrosine kinase inhibitor and is currently approved by the US Food and Drug Administration for patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, specifically targeting the BCR-ABL gene mutation, T315I. Due to ponatinib’s unique multi-targeted characteristics, further studies have demonstrated its ability to target other important tyrosine kinases (FGFR, PDGFR, SRC, RET, KIT, and FLT1) in other human malignancies. This review focuses on the available data of ponatinib and its molecular targets for treatment in various cancers, with a discussion on the broader potential of this agent in other cancer indications. Keywords: ponatinib, cancer treatment, multi-kinase inhibitor, repurposin

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