Ponatinib Combined With Rapamycin Causes Regression of Murine Venous Malformation

Abstract

Supplemental Digital Content is available in the text.

Ponatinib treatment promotes arterial thrombosis and hyperactive platelets

“…Because recent studies have indicated ponatinib influences vessels, 4,5,11 aortas were examined for evidence of increased reactive oxygen species (ROS) and apoptosis in treated mice by nitrotyrosine and caspase 3 expression, respectively. There was increased nitrotyrosine and caspase 3 expression in the adventitia of mice treated with either 15 or 3 mg/kg of ponatinib ( Figure 1B).…”

“…3 It inhibits ABL1 (T315I), fibroblast growth factor receptors 1 to 4, vascular endothelial growth factor receptors 1 to 3, FLT3, KIT, platelet-derived growth factor receptor, SRC, MEKK3, and Tie2, which are important vascular and myeloid cell receptors involved in cell growth, proliferation, angiogenesis, and repair. [3][4][5] ABL kinases (ABL1 and ABL2) themselves influence vascular development, function, and survival and regulate angiopoietin1/Tie2-mediated activities. 6,7 Loss of ABL1 kinase leads to vascular dysfunction, apoptosis, tissue damage, infarction, and microvascular thrombosis, and its deletion is embryonically lethal.…”

Venous Malformation of the Parotid Gland

“…To overcome imatinib resistance, adenosine triphosphate-competitive ABL kinase inhibitors were developed such as ponatinib, nilotinib, and bosutinib. 9 These drugs improved the efficacy and resistance of imatinib. ABL kinase inhibitor and mTOR are potent compounds decreasing HUVEC TIE2-L914F cell proliferation.…”

“…ABL kinase inhibitor and mTOR are potent compounds decreasing HUVEC TIE2-L914F cell proliferation. 9 Ponatinib with rapamycin is a novel targeted therapy to induce regression of venous malformation. 9 In spite of targeted therapy, sclerotherapy remains the easily available management option.…”

“…9 Ponatinib with rapamycin is a novel targeted therapy to induce regression of venous malformation. 9 In spite of targeted therapy, sclerotherapy remains the easily available management option. In this case, foam sclerotherapy was made using Tessari technique.…”