ArticleCancer biology & therapy2016
Antitumor effects and molecular mechanisms of ponatinib on endometrial cancer cells harboring activating FGFR2 mutations.
Article in Cancer biology & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- The Adverse Impact of Tyrosine Kinase Inhibitors on Wound Healing and Repair.International wound journal · 2025Review
- Developing New Peptides and Peptide-Drug Conjugates for Targeting the FGFR2 Receptor-Expressing Tumor Cells and 3D Spheroids.Biomimetics (Basel, Switzerland) · 2024Article
- m6A-related long noncoding RNAs predict prognosis and indicate therapeutic response in endometrial carcinoma.Journal of clinical laboratory analysis · 2023Article
- Ferroptosis-Related lncRNA for the Establishment of Novel Prognostic Signature and Therapeutic Response Prediction to Endometrial Carcinoma.BioMed research international · 2022Article
- Landscape of drug-resistance mutations in kinase regulatory hotspots.Briefings in bioinformatics · 2021Article
- Development of Biomarker Signatures Associated with Anoikis to Predict Prognosis in Endometrial Carcinoma Patients.Journal of oncology · 2021Article
- Diagnosis and treatment of mixed phenotype (T-myeloid/lymphoid) acute leukemia with novel ETV6-FGFR2 rearrangement.Blood advances · 2020Article
- Cardiotoxicity of the BCR-ABL1 tyrosine kinase inhibitors: Emphasis on ponatinib.International journal of cardiology · 2020Review
- The Suitability of FGF21 and FGF23 as New Biomarkers in Endometrial Cancer Patients.Diagnostics (Basel, Switzerland) · 2020Article
- Fibroblast growth factor receptor promotes progression of cutaneous squamous cell carcinoma.Molecular carcinogenesis · 2019Article
- Ponatinib Inhibits Proliferation and Induces Apoptosis of Liver Cancer Cells, but Its Efficacy Is Compromised by Its Activation on PDK1/Akt/mTOR Signaling.Molecules (Basel, Switzerland) · 2019Article
- SUN2: A potential therapeutic target in cancer.Oncology letters · 2019Review
- Ponatinib: a novel multi-tyrosine kinase inhibitor against human malignancies.OncoTargets and therapy · 2019Review
- Review
- Ponatinib exerts anti-angiogenic effects in the zebrafish and human umbilical vein endothelial cells via blocking VEGFR signaling pathway.Oncotarget · 2018Article
- Article
- Preclinical analysis of MTOR complex 1/2 inhibition in diffuse intrinsic pontine glioma.Oncology reports · 2018Article
- Clinical genomic profiling to identify actionable alterations for investigational therapies in patients with diverse sarcomas.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant mutational activation of FGFR2 is associated with endometrial cancers (ECs). AP24534 (ponatinib) currently undergoing clinical trials has been known to be an orally available multi-targeted tyrosine kinase inhibitor. Our biochemical kinase assay showed that AP24534 is potent against wild-type FGFR1-4 and 5 mutant FGFRs (V561M-FGFR1, N549H-FGFR2, K650E-FGFR3, G697C-FGFR3, N535K-FGFR4) and possesses the strongest kinase-inhibitory activity on N549H-FGFR2 (IC50 of 0.5 nM) among all FGFRs tested. We therefore investigated the effects of AP24534 on endometrial cancer cells harboring activating FGFR2 mutations and explored the underlying molecular mechanisms. AP24534 significantly inhibited the proliferation of endometrial cancer cells bearing activating FGFR2 mutations (N549K, K310R/N549K, S252W) and mainly induced G1/S cell cycle arrest leading to apoptosis. AP24534 also diminished the kinase activity of immunoprecipitated FGFR2 derived from MFE-296 and MFE-280 cells and reduced the phosphorylation of FGFR2 and FRS2 on MFE-296 and AN3CA cells. AP24534 caused substantial reductions in ERK phosphorylation, PLCγ signaling and STAT5 signal transduction on ECs bearing FGFR2 activating mutations. Akt signaling pathway was also deactivated by AP24534. AP24534 causes the chemotherapeutic effect through mainly the blockade of ERK, PLCγ and STAT5 signal transduction on ECs. Moreover, AP24534 inhibited migration and invasion of endometrial cancer cells with FGFR2 mutations. In addition, AP24534 significantly blocked anchorage-independent growth of endometrial cancer cells. We, for the first time, report the molecular mechanisms by which AP24534 exerts antitumor effects on ECs with FGFR2 activating mutations, which would provide mechanistic insight into ongoing clinical investigations of AP24534 for ECs.
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