Rapamycin may effectively treat patients with venous malformations.
A drug typically used to treat cancer has the ability to treat deformed blood vessels in patients with venous malformations (VMs), a recent study suggests.
Every 1 in 5000 individuals are born with VM, and since there is still no effective cure, researchers have been working towards finding an effective treatment.
A study published in Science Translational Medicine used genetically engineered mice with a PIK3CA mutation — a gene that’s been linked to cancer – and found that the mice had developed VM.
In order to verify the model, samples from 13 children with VM from UCL Institute of Child Health and 32 from MSK and Hospital de la Santa Creu i Sant Pau were genetically tested. Researchers discovered that about one-quarter of patients had the same type of PIK3CA mutation found in the mice.
Next, different drugs were tested on mice to find an effective treatment.
When using rapamycin, it was found that the drug blocked a signaling process that occurs downstream of PIK3CA. Although it has the ability to stop one of PIK3CA's effects, it does not block it directly at the source.
“When we gave rapamycin to the mice, it showed clinical benefit, but in patients it can have serious side effects and compromise the immune system,” said lead author Sandra Castillo.
At MSK, cancer drugs were tested that directly inhibit PIK3CA. The results of the study showed the drugs significantly reduced the size of malformations when administered through the bloodstream and when applied directly to the skin in cream form.
“It is incredibly exciting to have stumbled across new treatment options for these blood vessel disorders, essentially by accident,” said senior author Bart Vanhaesebroeck. “It's still not clear why this mutation causes VM instead of cancer in these patients, so further research in this area could offer valuable insights into how to stop tissue from becoming cancerous.”
The topical skin cream could provide a better targeted approach for treating VMs, because it does not enter the bloodstream and therefore causes negative side effects, but further research needs to be conducted before it is tested on humans.
“This paper supports the theory that blood vessels are much more sensitive to PIK3CA than other cells,” said senior co-author Mariona Graupera. “We have previously looked at what happens when PIK3CA is inactivated, but here we saw that an activating mutation in this gene can lead to a dramatic overgrowth of blood vessels. In cancer, tumors need to form new blood vessels so that they can survive and spread. Drugs to stop these processes and starve the tumors are currently in clinical trials, and we now hope that such drugs may also have a role to play in treating VM.”