PIK3CA mutations in vascular malformations

Curr Opin Hematol. 2019 May;26(3):170-178. doi: 10.1097/MOH.0000000000000496.


Purpose of review: Recently, it has been discovered that a subset of vascular malformations, of the lymphatic and venous type, are caused by oncogenic mutations in the PIK3CA gene. Now, efforts have been focused in the understanding of the molecular and cellular consequences of these mutations and the opportunities for novel-targeted therapies for these diseases.

Recent findings: Here, we review the latest findings in the biology of oncogenic PIK3CA mutations in the pathogenesis of vascular malformations. We focus on the recent development of in-vitro and in-vivo tools for the study of PIK3CA-mutant vascular malformations with special interest in preclinical models for drug testing. Also, we review the latest advances in phosphoinositide 3-kinase (PI3K) inhibitors in the clinic and their repurposing for the treatment of lymphatic malformations and venous malformations.

Summary: Oncogenic mutations on PIK3CA causing lymphatic malformations and venous malformations are also frequently found in epithelial cancer. Thus, fundamental research done in the cancer field during the past decades might be applied to the understanding of lymphatic malformations and venous malformations. Likewise, repurposing PI3K pathway inhibitors that are currently in cancer clinical trials can be used as a novel strategy for the treatment of these diseases. Here, we also open a debate for the consideration of lymphatic malformations and venous malformations as developmental tumours.

Publication types

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

MeSH terms

  • Animals
  • Class I Phosphatidylinositol 3-Kinases* / antagonists & inhibitors
  • Class I Phosphatidylinositol 3-Kinases* / genetics
  • Class I Phosphatidylinositol 3-Kinases* / metabolism
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Mutation*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms, Glandular and Epithelial / drug therapy
  • Neoplasms, Glandular and Epithelial / epidemiology
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / pathology
  • Signal Transduction* / drug effects
  • Signal Transduction* / genetics
  • Vascular Malformations* / drug therapy
  • Vascular Malformations* / enzymology
  • Vascular Malformations* / genetics
  • Vascular Malformations* / pathology


  • Enzyme Inhibitors
  • Neoplasm Proteins
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human