title: Phase I clinical, pharmacokinetic, and pharmacodynamic study of the Akt-inhibitor triciribine phosphate monohydrate in patients with advanced hematologic malignancies.
abstract: Akt, a serine/threonine protein kinase, is constitutively phosphorylated and hyperactivated in multiple cancers, including acute myeloid leukemia. High levels are linked to poor survival and inferior responses to chemotherapy, making Akt inhibition an attractive therapeutic target. In this phase I/II study of TCN-PM, a small-molecule Akt inhibitor, TCN-PM therapy was well tolerated in patients with advanced hematological malignancies, and reduced levels of phosphorylation of Akt and its substrate Bad were shown, consistent with inhibition of this survival pathway and induction of cell death. Further investigation of TCN-PM alone or in combination in patients with high Akt levels is warranted.
authors.affiliation: Departments of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Sampath
authors.forename: Asifa
authors.initials: A
authors.lastname: Malik
authors.forename: William
authors.initials: W
authors.lastname: Plunkett
authors.forename: Billie
authors.initials: B
authors.lastname: Nowak
authors.forename: Betsy
authors.initials: B
authors.lastname: Williams
authors.forename: Michelle
authors.initials: M
authors.lastname: Burton
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Alan F
authors.initials: AF
authors.lastname: List
authors.forename: Said
authors.initials: S
authors.lastname: Sebti
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lancet
mesh_terms: D000073:Acenaphthenes / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D012265:Ribonucleotides / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D000073:Acenaphthenes; D012265:Ribonucleotides; C014205:triciribine phosphate; D051057:Proto-Oncogene Proteins c-akt
keywords: AML; Akt; Nucleoside analog; Phase I clinical trial; Triciribine