Targeted management of vascular anomalies

Area of Science:

• Genetics
• Molecular Biology
• Pharmacology

Background:

• Vascular anomalies are often linked to genetic variants affecting key signaling pathways.
• The PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways are frequently implicated in vascular anomaly pathogenesis.
• Previously, effective treatments for these rare conditions were limited.

Purpose of the Study:

• To review the genetic underpinnings of vascular anomalies.
• To synthesize current knowledge on targeted therapeutic strategies based on genetic pathways.
• To highlight the shift towards personalized, genotype-guided management.

Main Methods:

• A narrative review of existing literature.
• Literature search conducted across PubMed, Google Scholar, and EMBASE.
• Focus on genetic pathways and emerging therapies for vascular anomalies.

Main Results:

• mTOR inhibitors demonstrate efficacy across various vascular malformations.
• PIK3CA inhibitors are utilized for PIK3CA-related overgrowth spectrum (PROS).
• Ongoing trials for AKT, MEK, and BRAF inhibitors in specific vascular anomalies like Proteus syndrome and arteriovenous malformations.

Conclusions:

• Identification of molecular pathways has revolutionized vascular anomaly treatment.
• Repurposing existing drugs enables genotype-guided, personalized patient care.
• Targeted therapies represent a significant advancement for previously orphan diseases.