Combination therapies for overcoming resistance to mitotic agents during chemotherapy

A pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a compound comprising Formula I,

• salts, esters, prodrugs, or derivatives thereof wherein,
• A is a carbocyclyl, aryl, or heterocyclyl, wherein A is optionally substituted with one or more, the same or different, R20;
• X1, X2, and X3 are each O or S;
• R1 is a heterocyclyl or heterocyclyl comprising a nitrogen containing five membered ring wherein the nitrogen is substituted with benzyl wherein R1 is optionally substituted with one or more, the same or different, R20;
• R2 is hydrogen, alkyl, amino, formyl, carboxy, carbamoyl, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R2 is optionally substituted with one or more, the same or different, R20;
• R20 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R20 is optionally substituted with one or more, the same or different, R21;
• and
• R21 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.