Effective treatment of tumors and cancer with triciribine and related compounds

A method of treating a tumor or cancer in a patient, wherein the tumor or cancer is of the pancreas, ovary or colon, and wherein the tumor or cancer has enhanced sensitivity to triciribine (TCN) comprising:

• administering to the patient at least one compound of the formula:
• wherein each R2′, R3′, and R5′ are independently hydrogen, optionally substituted phosphate or phosphonate;
• acyl;
• alkyl;
• amide, sulfonate ester;
• sulfonyl, wherein the phenyl group is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, or phosphonate;
• optionally substituted arylsulfonyl;
• a lipid;
• a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• or cholesterol;
• or other pharmaceutically acceptable leaving group that, in vivo, provides a compound wherein R2′, R3′, and R5′ is independently H or mono-, di- or tri-phosphate;
• wherein Rx and Ry are independently hydrogen, optionally substituted phosphate;
• acyl;
• amide, alkyl;
• aromatic, polyoxyalkylene optionally substituted arylsulfonyl;
• a lipid;
• a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• or cholesterol;
• or other pharmaceutically acceptable leaving group;
• R1 and R2 each are independently H, optionally substituted straight chained, branched or cyclic alkyl, alkenyl, or alkynyl, CO-alkyl, CO-alkenyl, CO-alkynyl, CO-aryl or heteroaryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, sulfonyl, alkylsulfonyl, arylsulfonyl, or aralkylsulfonyl;
• and
• wherein at least 10 mg/m2 of the compound is administered by intravenous infusion one time per week.

A method for identifying and treating a patient having a tumor or cancer cell with enhanced sensitivity to triciribine (TCN), wherein the tumor or cancer is of the pancreas, ovary or colon, in a mammal comprising:

• (a) determining whether a patient has a tumor or cancer cell with enhanced sensitivity to triciribine comprising:
• (i) obtaining a biological sample of the tumor or cancer cell from the patient;
• (ii) measuring the expression level of Akt kinase from the tumor or cancer cell from the patient;
• and
• (iii) comparing the expression level of Akt kinase from the tumor or cancer cell to the expression level in a control tissue,
• wherein a 1.5-fold greater expression of Akt in the tumor or cancer cell compared to a control tissue is indicative of a patient having a tumor or cancer cell with enhanced sensitivity to triciribine;
• and
• (b) administering to the mammal at least one compound selected from the group consisting of:
• wherein each R2′, R3′, and R5′ are independently hydrogen, optionally substituted phosphate or phosphonate;
• acyl;
• alkyl;
• amide, sulfonate ester;
• sulfonyl, wherein the phenyl group is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, or phosphonate;
• optionally substituted arylsulfonyl;
• a lipid;
• a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• or cholesterol;
• or other pharmaceutically acceptable leaving group that, in vivo, provides a compound wherein R2′, R3′, and R5′ is independently H or mono-, di- or tri-phosphate;
• wherein Rx and Ry are independently hydrogen, optionally substituted phosphate;
• acyl;
• amide, alkyl;
• aromatic, polyoxyalkylene optionally substituted arylsulfonyl;
• a lipid;
• a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• or cholesterol;
• or other pharmaceutically acceptable leaving group;
• R1 and R2 each are independently H, optionally substituted straight chained, branched or cyclic alkyl, alkenyl, or alkynyl, CO-alkyl, CO-alkenyl, CO-alkynyl, CO-aryl or heteroaryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, sulfonyl, alkylsulfonyl, arylsulfonyl, or aralkylsulfonyl;
• and
• wherein at least 10 mg/m2 of the compound is administered over a one-hour intravenous infusion with a dosing regimen of one time per week for three weeks.