| 摘要 |
The inventors have determined, contrary to the prior art and experience, how to successfully use triciribine to treat ovarian cancer by one or a combination of (i) administering triciribine only to patients which according to a diagnostic test described below, exhibit enhanced sensitivity to the drug; (ii) use of a described dosage level that minimizes the toxicity of the drug but yet still exhibits efficacy; or (iii) use of a described dosage regimen that minimizes the toxicity of the drug. The invention further encompasses a number of miRNAs, which are altered in human ovarian cancer, with the most significantly deregulated miRNAs being miR-214, -199a*, -200a, -100, -12Sb, and let-7 cluster. Further, the invention illustrates that frequent deregulation of miR-214, -199a*, -200a and -100 in ovarian cancers and their alterations are associated with high grade and late stage tumor. |
| 主权项 |
1. A method for treating ovarian cancer in a mammal comprising:
(i) obtaining a biological sample from the tumor or cancer; (ii) determining whether the tumor or cancer overexpresses an Akt kinase, and (iii) if the tumor or cancer overexpresses Akt kinase, administering to said mammal a dose of 10 mg/m2 or less of at least one compound of the formula: wherein each R2′, R3′ and R5′ are independently hydrogen, optionally substituted phosphate or phosphate; acyl; alkyl; amide, sulfonate ester; sulfonyl; methanesulfonyl; benzylsulfonyl, wherein the phenyl group is optionally substituted with one or more substituents; optionally substituted arylsulfonyl; a lipid, 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′ or 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; polyethyleneglycol optionally substituted arylsulfonyl, a lipid, phospholipid; an amino acid; a carbohydrate; a peptide; or cholesterol; or other pharmaceutically acceptable leaving group; wherein 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, aralkylsulfonyl. |
