Use of phosphoinositide 3-kinase inhibitors for treatment of vascular malformations

Abstract

The present disclosure relates to methods of treating a vascular malformation in a subject expressing a gain-of-function mutation in a PIK3CA gene comprising administering, to the subject, an effective amount of an agent that inhibits phosphoinositide 3-kinase (“PI3K”).

What is claimed is: 
     
         1 . A method of treating a venous malformation in a subject in need thereof, comprising providing to the subject an effective amount of a compound having CAS Registry No. 371943-05-4 represented by the formula: 
       
         
           
           
               
               
           
         
       
     
     
         2 . The method of  claim 1 , wherein the subject has a gain-of-function mutation in the PI3K/AKT pathway. 
     
     
         3 . The method of  claim 1 , wherein the gain-of-function mutation is an activating mutation of PIK3CA, or a mutation in at least one of AKT1, AKT2, AKT3, and IRS2. 
     
     
         4 . The method of  claim 3 , wherein the activating mutation is selected from the group consisting of R88Q, E542K, E545K, E545Q, H1047L, H1047Q, H1047R, C420R, and I143V. 
     
     
         5 . The method of  claim 1 , wherein the venous malformation is located in the brain, and/or within the skin. 
     
     
         6 . The method of  claim 1 , wherein:
 a) the subject suffers from multiple venous malformations, a malignancy, a multisystem genetic disorder, or a combination thereof or   b) the surgical treatment of the venous malformation would be high-risk.   
     
     
         7 . The method of  claim 1 , wherein the venous malformation is a sporadic venous malformation. 
     
     
         8 . The method of  claim 1 , wherein the compound is provided systemically or locally. 
     
     
         9 . The method of  claim 1 , wherein the compound is provided topically. 
     
     
         10 . The method of  claim 1 , wherein the compound is provided to the venous malformation or a portion thereof. 
     
     
         11 . The method of  claim 10 , wherein the compound is topically provided to the venous malformation or a portion thereof. 
     
     
         12 . The method of  claim 1 , wherein the compound is provided by administering the compound parenterally. 
     
     
         13 . The method of  claim 1 , wherein the compound is provided by administering the compound orally. 
     
     
         14 . The method of  claim 1 , further comprising administering to the subject a second agent that inhibits the PI3K/AKT pathway, wherein the second agent is in an amount that, together with the agent of  claim 1 , effectively treats the venous malformation.