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Updated: Jan 30, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Ponatinib: a novel multi-tyrosine kinase inhibitor against human malignancies
Fiona H Tan1,2, Tracy L Putoczki1,3,4, Stanley S Stylli1,5
1Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia, rluwor@unimelb.edu.au.
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.
Insights
Ponatinib is a multi-tyrosine kinase inhibitor approved for certain leukemias. Its ability to target multiple kinases suggests potential for treating various human malignancies beyond its current indications.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Aberrant tyrosine kinase activity drives many human malignancies.
- Key kinases like EGFR, FGFR, PDGFR, and VEGFR are implicated in common cancers.
- Ponatinib (AP24534) is an FDA-approved multi-tyrosine kinase inhibitor for specific leukemias targeting BCR-ABL T315I.
Purpose of the Study:
- To review available data on ponatinib and its molecular targets.
- To discuss the potential of ponatinib in treating various cancers.
- To explore broader applications of ponatinib in other cancer indications.
Main Methods:
- Review of existing scientific literature and clinical data on ponatinib.
- Analysis of ponatinib's molecular targeting profile.
- Discussion of preclinical and clinical findings for ponatinib in diverse malignancies.
Main Results:
- Ponatinib targets BCR-ABL, including the T315I mutation, in approved leukemia indications.
- Ponatinib demonstrates activity against other tyrosine kinases such as FGFR, PDGFR, SRC, RET, KIT, and FLT1.
- Emerging data suggests ponatinib's efficacy in various human malignancies beyond leukemia.
Conclusions:
- Ponatinib's multi-targeted nature offers therapeutic potential in a range of cancers.
- Further investigation into ponatinib's efficacy across different malignancies is warranted.
- Ponatinib represents a promising agent for expanding treatment options in oncology.
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