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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Veröffentlicht in:OncoTargets and therapy 2019-01, Vol.12, p.635-645
Hauptverfasser: Tan, Fiona H, Putoczki, Tracy L, Stylli, Stanley S, Luwor, Rodney B
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Sprache:eng
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Zusammenfassung: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.
ISSN:1178-6930
1178-6930
DOI:10.2147/OTT.S189391