Phosphoinositide 3-kinase: a new kid on the block in vascular anomalies

J Pathol. 2016 Dec;240(4):387-396. doi: 10.1002/path.4802. Epub 2016 Oct 20.

Abstract

Vascular anomalies are broadly divided into vascular tumours and malformations. These lesions are composed of abnormal vascular elements of various types, and mainly affect infants, children, and young adults. Vascular anomalies may be painful, may be complicated by bleeding, infection, or organ dysfunction, and can have secondary effects on other tissues. Current treatment strategies include surgical excision, pulsed laser, and sclerotherapy, which are invasive, with risks of recurrence. There are growing pharmacological options for these vascular anomalies, but, to date, no specific targeted therapies have been developed. Phosphoinositide 3-kinases (PI3Ks) constitute a family of lipid kinases that are involved in signal transduction and vesicular traffic, and that modulate important cellular processes such as proliferation, growth, and migration. Recent findings have indicated that the PI3K signalling pathway is important in the pathogenesis of vascular anomalies. This provides an opportunity to use PI3K inhibitors, which are in clinical trials for cancer treatment, for such lesions. Here, we provide an update on the classification of vascular anomalies, with their major features, and discuss the role of the PI3K signalling pathway in the pathogenesis of vascular anomalies, and their clinical implications and therapeutic opportunities. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: AKT; PI3K; mTOR; signal transduction; targeted therapy; vascular anomaly; vascular malformation; vascular tumour.

Publication types

  • Review

MeSH terms

  • Humans
  • Molecular Targeted Therapy / methods
  • Phosphatidylinositol 3-Kinases / physiology*
  • Phosphoinositide-3 Kinase Inhibitors
  • Signal Transduction / physiology
  • Vascular Malformations / classification
  • Vascular Malformations / enzymology*
  • Vascular Malformations / pathology
  • Vascular Malformations / therapy
  • Vascular Neoplasms / classification
  • Vascular Neoplasms / enzymology*
  • Vascular Neoplasms / pathology
  • Vascular Neoplasms / therapy

Substances

  • Phosphoinositide-3 Kinase Inhibitors