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Two research teams have found evidence to suggest that mutations in PIK3CA, a gene linked to cancer, may drive venous malformations (VMs) in some patients.
Both groups of researchers showed that PIK3CA mutations give rise to VMs in mice, and PIK3CA mutations are present in humans with VMs.
Subsequent experiments with the mice suggested that PIK3CA inhibitors could be used to treat VMs.
Both groups reported their findings in Science Translational Medicine.
Pau Castel, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues were originally studying the role of PIK3CA in uterine cancer when they noticed that mice harboring PIK3CA mutations developed defective blood vessels that closely resembled VMs.
Sandra Castillo, PhD, of University College London in the UK, and her colleagues generated mice with PIK3CA-activating mutations that also mimicked the human disease, including during mouse embryonic development.
Both teams found the mutations spurred uncontrolled growth of endothelial cells, which formed abnormal clusters and faulty blood vessels.
To verify their mouse models, the researchers analyzed samples from patients with VMs. Dr Castillo and her colleagues looked at samples from 13 children, while Castel and his colleagues evaluated samples from 32 patients (both adults and children).
Dr Castillo and her colleagues found PIK3CA mutations in 25% of patients, and Castel and his colleagues found mutations in PIK3CA and related genes of the PI3K/AKT pathway in about 30% of patients.
Both groups of researchers then tested PI3K inhibitors in their mouse models and found these drugs could stunt blood vessel overgrowth.
“Rapamycin is a drug that blocks a signaling process that happens downstream of PIK3CA, so it stops one of PIK3CA’s effects but does not block it at the source,” Dr Castillo said. “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.”
“Our colleagues at MSK [Memorial Sloan Kettering] then tested drugs on the mice that directly inhibit PIK3CA, developed to treat cancer. These drugs worked well and significantly reduced the size of the malformations, not only when given through the bloodstream but also when applied directly to the skin as a cream.” 
Photo by Aaron Logan
Two research teams have found evidence to suggest that mutations in PIK3CA, a gene linked to cancer, may drive venous malformations (VMs) in some patients.
Both groups of researchers showed that PIK3CA mutations give rise to VMs in mice, and PIK3CA mutations are present in humans with VMs.
Subsequent experiments with the mice suggested that PIK3CA inhibitors could be used to treat VMs.
Both groups reported their findings in Science Translational Medicine.
Pau Castel, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues were originally studying the role of PIK3CA in uterine cancer when they noticed that mice harboring PIK3CA mutations developed defective blood vessels that closely resembled VMs.
Sandra Castillo, PhD, of University College London in the UK, and her colleagues generated mice with PIK3CA-activating mutations that also mimicked the human disease, including during mouse embryonic development.
Both teams found the mutations spurred uncontrolled growth of endothelial cells, which formed abnormal clusters and faulty blood vessels.
To verify their mouse models, the researchers analyzed samples from patients with VMs. Dr Castillo and her colleagues looked at samples from 13 children, while Castel and his colleagues evaluated samples from 32 patients (both adults and children).
Dr Castillo and her colleagues found PIK3CA mutations in 25% of patients, and Castel and his colleagues found mutations in PIK3CA and related genes of the PI3K/AKT pathway in about 30% of patients.
Both groups of researchers then tested PI3K inhibitors in their mouse models and found these drugs could stunt blood vessel overgrowth.
“Rapamycin is a drug that blocks a signaling process that happens downstream of PIK3CA, so it stops one of PIK3CA’s effects but does not block it at the source,” Dr Castillo said. “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.”
“Our colleagues at MSK [Memorial Sloan Kettering] then tested drugs on the mice that directly inhibit PIK3CA, developed to treat cancer. These drugs worked well and significantly reduced the size of the malformations, not only when given through the bloodstream but also when applied directly to the skin as a cream.”
Photo by Aaron Logan
Two research teams have found evidence to suggest that mutations in PIK3CA, a gene linked to cancer, may drive venous malformations (VMs) in some patients.
Both groups of researchers showed that PIK3CA mutations give rise to VMs in mice, and PIK3CA mutations are present in humans with VMs.
Subsequent experiments with the mice suggested that PIK3CA inhibitors could be used to treat VMs.
Both groups reported their findings in Science Translational Medicine.
Pau Castel, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues were originally studying the role of PIK3CA in uterine cancer when they noticed that mice harboring PIK3CA mutations developed defective blood vessels that closely resembled VMs.
Sandra Castillo, PhD, of University College London in the UK, and her colleagues generated mice with PIK3CA-activating mutations that also mimicked the human disease, including during mouse embryonic development.
Both teams found the mutations spurred uncontrolled growth of endothelial cells, which formed abnormal clusters and faulty blood vessels.
To verify their mouse models, the researchers analyzed samples from patients with VMs. Dr Castillo and her colleagues looked at samples from 13 children, while Castel and his colleagues evaluated samples from 32 patients (both adults and children).
Dr Castillo and her colleagues found PIK3CA mutations in 25% of patients, and Castel and his colleagues found mutations in PIK3CA and related genes of the PI3K/AKT pathway in about 30% of patients.
Both groups of researchers then tested PI3K inhibitors in their mouse models and found these drugs could stunt blood vessel overgrowth.
“Rapamycin is a drug that blocks a signaling process that happens downstream of PIK3CA, so it stops one of PIK3CA’s effects but does not block it at the source,” Dr Castillo said. “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.”
“Our colleagues at MSK [Memorial Sloan Kettering] then tested drugs on the mice that directly inhibit PIK3CA, developed to treat cancer. These drugs worked well and significantly reduced the size of the malformations, not only when given through the bloodstream but also when applied directly to the skin as a cream.”