Dianhydrogalactitol for the treatment of diffuse intrinsic pontine gliomas

Abstract

A method for treating diffuse intrinsic pontine glioma (DIPG) including administering a therapeutically effective quantity of an alkylating hexitol alone or in combination with another antiproliferative agent, such as an inhibitor of Wee1 tyrosine kinase, is disclosed.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 
     
         1 . A method of suppressing proliferation of a diffuse intrinsic pontine glioma (DIPG) cell, the method comprising administering to the DIPG cell an alkylating hexitol derivative. 
     
     
         2 . The method of  claim 1 , wherein the alkylating hexitol derivative is dianhydrogalactitol, diacetyldianhydrogalactitol, ordibromodulcitol. 
     
     
         3 . The method of  claim 1 , wherein the alkylating hexitol derivative is dianhydrogalactitol. 
     
     
         4 . The method of  claim 1 , wherein the DIPG cell is in a human subject. 
     
     
         5 . The method of  claim 4 , wherein the human subject is a pediatric patient. 
     
     
         6 . The method of  claim 1 , wherein the administering is done in vivo. 
     
     
         7 . The method of  claim 6 , wherein the administering is done in vivo in a human subject by administering a therapeutically effective quantity of the alkylating hexitol derivative to the human subject. 
     
     
         8 . The method of  claim 1 , wherein the method further comprises administering a therapeutically effective quantity of an agent that requires malignant cells to be in the S/G2 phase of the cell cycle for its maximum therapeutic effect. 
     
     
         9 . The method of  claim 1 , wherein the method further comprises administering a therapeutically effective quantity of an inhibitor of Wee1 tyrosine kinase. 
     
     
         10 . The method of  claim 9 , wherein the inhibitor of Wee1 tyrosine kinase is AZD1775. 
     
     
         11 . The method of  claim 1 , wherein the DIPG cell comprises a p53-mutation, a histone H3.3 K27M mutation, a histone H3.1 K27M mutation, or a combination of the p53 mutation and the histone H3.3 K27M mutation. 
     
     
         12 . The method of  claim 9 , wherein the alkylating hexitol derivative and the inhibitor of Wee1 tyrosine kinase are administered in any sequential order. 
     
     
         13 . The method of  claim 9 , wherein the alkylating hexitol derivative and the inhibitor of Wee1 tyrosine kinase are administered on different days. 
     
     
         14 . The method of  claim 9 , wherein the alkylating hexitol derivative and the inhibitor of Wee1 tyrosine kinase are administered on the same days.