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

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,...

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Published inOncoTargets and therapy Vol. 12; pp. 635 - 645
Main Authors Tan, Fiona H, Putoczki, Tracy L, Stylli, Stanley S, Luwor, Rodney B
Format Journal Article
LanguageEnglish
Published New Zealand Dove Medical Press Limited 01.01.2019
Taylor & Francis Ltd
Dove Medical Press
Subjects
Antimitotic agents
Antineoplastic agents
Cancer
cancer treatment
Chromosomes
Development and progression
Drug approval
Gastrointestinal cancer
Gene mutations
Genetic aspects
Kinases
Lung cancer, Non-small cell
Mediation
Multi-kinase inhibitor
Mutation
Nilotinib
Phenols
Ponatinib
re-purposing
Review
Targeted cancer therapy
Thyroid cancer
Tyrosine
Vascular endothelial growth factor
Australia
Pennsylvania
United States > US
multi-kinase inhibitor
cancer treatment
ponatinib
repurposing
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Summary: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.
Bibliography:ObjectType-Article-2
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ISSN:1178-6930
1178-6930
DOI:10.2147/OTT.S189391