This is a summary of the article written by Emmanuel Seront, An Van Damme, Julien Coulie, Laurence M Boon & Miikka Vikkula.
This article explains:
- What vascular malformations are (abnormalities in blood vessels).
- Why they occur (genetic mutations).
- Why traditional treatments are often not sufficient.
- And especially: new medications that target the underlying cause.
What are vascular malformations?
These are congenital abnormalities of blood vessels. The vessels are structured differently than normal.
Important:
- They are usually present at birth.
- They often grow slowly over time.
These can cause symptoms such as:
- Pain.
- Swelling.
- Bleeding.
- Reduced function.
Types
- Slow-flow: venous, lymphatic, capillary.
- Fast-flow: arteriovenous.
Why they are difficult to treat?
Traditional treatments:
- Surgery.
- Embolization (blocking vessels).
- Sclerotherapy (injecting a substance into the vessels).
Problem:
- Often not fully effective.
- Malformation can recur.
- Difficult to treat large or complex areas.
The real cause: Errors in cells
The key discovery: these conditions are caused by genetic changes in blood vessel cells.
These errors cause the cells to grow excessively and receive incorrect signals.
Key “signaling pathways”
You can think of them as the cell’s gas pedals:
[Signal] → [Growth pathway] → [Cell grows]
Main pathways:
- PI3K → AKT → mTOR.
- RAS → MAPK → ERK.
If these “on-switches” get stuck → the vessel grows abnormally.
Simple diagram:
Normal:
Signal → ON → OFF → controlled growth.
In malformation:
Signal → ON → ON → ON → overgrowth.
New treatments (key part of the article)
Instead of relying solely on surgery, doctors are now trying to inhibit the cause within the cells using medications.
Sirolimus (key medication)
Works on: mTOR-pad.
Effect:
- Inhibits the growth of abnormal vessels.
- Reduces symptoms.
- Improves quality of life.
It is often used for venous malformations and lymphatic malformations.
PI3K-Inhibitors
- Even more targeted than sirolimus.
- Especially for specific genetic mutations (such as PIK3CA).
Advantage: potentially more effective.
Disadvantage: still limited long-term data.
MEK-Inhibitors
- They act on the other pathway (RAS/MAPK).
- Used for fast-flow malformations (AVM).
- Anti-angiogenesis drugs inhibit the formation of new blood vessels.
- Examples include Bevacizumab and Thalidomide.
- Used, among others, for hereditary bleeding disorders.
Overview treatments
- Genetic problem → Targeted therapy.
- PI3K mutation → sirolimus / PI3K inhibitor.
- RAS mutation → MEK inhibitor.
- Excessive vessel growth → anti-angiogenesis.
Combination of treatments
Key insight
The new approach is NOT just medication or surgery alone, but:
Medication + surgery + embolization = best results.
Future: “Precision medicine”
Doctors increasingly start by identifying the genetic problem and then choosing a personalized treatment:
- Step 1: DNA analysis.
- Step 2: select the appropriate medication.
- Step 3: evaluate and adjust.
Challenges
There are still challenges:
- Genetic testing is not available everywhere.
- Medications can be expensive or not covered by insurance.
- Side effects (e.g., skin issues, metabolic problems).
- Limited long-term knowledge.
Key message of this article
Before: focus on treating symptoms.
Now: focus on treating the cause (within the cells).
Goal: not always cure, but disease control with improved quality of life.
Summary
- Vascular malformations = congenital abnormalities of blood vessels.
- Cause = genetic errors in cells.
- Old treatments often do not work completely.
- New therapies target molecular processes.
- Future = personalized treatment based on DNA.
Article citation: Emmanuel Seront, An Van Damme, Julien Coulie, Laurence M Boon & Miikka Vikkula (17 Mar 2026): Current and emerging pharmacotherapies for treating vascular malformations, Expert Review of Clinical Pharmacology, DOI: 10.1080/17512433.2026.2641807
Link to full article: https://doi.org/10.1080/17512433.2026.2641807
