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PIK3CA mutations in vascular malformations

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Purpose of the 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 PI3K inhibitors in the clinic and their repurposing for the treatment of lymphatic malformations (LMs) and venous malformations (VMs). Summary: Oncogenic mutations on PIK3CA causing LMs and VMs 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 LMs and VMs. 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 LMs and VMs as developmental tumours.

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CASTILLO, Sandra d., BASELGA TORRES, Eulalia, GRAUPERA I GARCIA-MILÀ, Mariona. PIK3CA mutations in vascular malformations. _Current Opinion in Hematology_. 2019. Vol. 26, núm. 3, pàgs. 170-178. [consulta: 27 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/174064]

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