Genetic Basis and Therapies for Vascular Anomalies

Circ Res. 2021 Jun 25;129(1):155-173. doi: 10.1161/CIRCRESAHA.121.318145. Epub 2021 Jun 24.

Abstract

Vascular and lymphatic malformations represent a challenge for clinicians. The identification of inherited and somatic mutations in important signaling pathways, including the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin), RAS (rat sarcoma)/RAF (rapidly accelerated fibrosarcoma)/MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinases), HGF (hepatocyte growth factor)/c-Met (hepatocyte growth factor receptor), and VEGF (vascular endothelial growth factor) A/VEGFR (vascular endothelial growth factor receptor) 2 cascades has led to the evaluation of tailored strategies with preexisting cancer drugs that interfere with these signaling pathways. The era of theranostics has started for the treatment of vascular anomalies. Registration: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001703-32.

Keywords: endothelium; mutation; precision medicine; sirolimus; thalidomide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Blood Vessels / abnormalities*
  • Blood Vessels / drug effects*
  • Blood Vessels / metabolism
  • Genetic Predisposition to Disease
  • Humans
  • Molecular Targeted Therapy
  • Mutation*
  • Neovascularization, Physiologic / drug effects*
  • Phenotype
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction
  • Vascular Malformations / drug therapy*
  • Vascular Malformations / genetics*
  • Vascular Malformations / metabolism
  • Vascular Malformations / pathology

Substances

  • Angiogenesis Inhibitors
  • Protein Kinase Inhibitors

Associated data

  • EudraCT/2015-001703-32