ArticleArteriosclerosis, thrombosis, and vascular biology2019
Ponatinib Combined With Rapamycin Causes Regression of Murine Venous Malformation.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Review
- Multifocal Sporadic Venous Malformations in a Child Caused by a Novel Somatic Double Mutation of the TEK Gene: A Case Report and Literature Review.Molecular genetics & genomic medicine · 2026Review
- Polymeric rapamycin nanoparticles encapsulating ponatinib cause regression of venous malformations in mice.Science translational medicine · 2026Article
- A human endothelial and adipose stem cell-based co-culture model for venous malformations.Angiogenesis · 2026Article
- Bleomycin ElectroScleroTherapy (BEST): mechanistic parallels to electrochemotherapy, experimental models, and unresolved questions.Radiology and oncology · 2026Review
- Semaphorin 3A and 3F Promote Lumen Expansion in TIE2-Mutated Venous Malformation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- EndothelialFrontiers in cell and developmental biology · 2025Article
- Venous Malformations: Unraveling Latest Mechanisms and Bridging Gaps in Targeted Therapy Development.International journal of biological sciences · 2025Review
- Size-dependent Nanoparticle Accumulation In Venous Malformations.Journal of vascular anomalies · 2024Article
- NRASPediatric blood & cancer · 2024Article
- Nilotinib-induced alterations in endothelial cell function recapitulate clinical vascular phenotypes independent of ABL1.Scientific reports · 2024Article
- SH2 domain protein E and ABL signaling regulate blood vessel size.PLoS genetics · 2024Article
- Reengineering Ponatinib to Minimize Cardiovascular Toxicity.Cancer research · 2022Article
- How we approach the use of sirolimus and new agents: Medical therapy to treat vascular anomalies.Pediatric blood & cancer · 2022Article
- NRASAngiogenesis · 2022Article
- A Xenograft Model for Venous Malformation.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Ponatinib and other CML Tyrosine Kinase Inhibitors in Thrombosis.International journal of molecular sciences · 2020Review
- Somatic Gain of KRAS Function in the Endothelium Is Sufficient to Cause Vascular Malformations That Require MEK but Not PI3K Signaling.Circulation research · 2020Article
- A Patient-Derived Xenograft Model for Venous Malformation.Journal of visualized experiments : JoVE · 2020Article
- Venous Malformation of the Parotid Gland.The International journal of angiology : official publication of the International College of Angiology, Inc · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Objective- Venous malformations (VMs) arise from developmental defects of the vasculature and are characterized by massively enlarged and tortuous venous channels. VMs grow commensurately leading to deformity, obstruction of vital structures, bleeding, and pain. Most VMs are associated with the activating mutation L914F in the endothelial cell (EC) tyrosine kinase receptor TIE2. Therapeutic options for VM are limited and ineffective while therapy with the mammalian target of rapamycin inhibitor rapamycin shows moderate efficacy. Here, we investigated novel therapeutic targets promoting VM regression. Approach and Results- We performed an unbiased screen of Food and Drug Administration-approved drugs in human umbilical vein ECs expressing the TIE2-L914F mutation (HUVEC-TIE2-L914F). Three ABL (Abelson) kinase inhibitors prevented cell proliferation of HUVEC-TIE2-L914F. Moreover, c-ABL, common target of these inhibitors, was highly phosphorylated in HUVEC-TIE2-L914F and VM patient-derived ECs with activating TIE2 mutations. Knockdown of c-ABL/ARG in HUVEC-TIE2-L914F reduced cell proliferation and vascularity of murine VM. Combination treatment with the ABL kinase inhibitor ponatinib and rapamycin caused VM regression in a xenograft model based on injection of HUVEC-TIE2-L914F. A reduced dose of this drug combination was effective in this VM murine model with minimal side effects. The drug combination was antiproliferative, enhanced cell apoptosis and vascular channel regression both in vivo and in a 3-dimensional fibrin gel assay. Conclusions- This is the first report of a combination therapy with ponatinib and rapamycin promoting regression of VM. Mechanistically, the drug combination enhanced AKT inhibition compared with single drug treatment and reduced PLCγ (phospholipase C) and ERK (extracellular signal-regulated kinase) activity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.