Abstract LB-293: Phase II study of the oral AKT inhibitor, MK-2206, for acute myeloid leukemia (AML) in second relapse
| Autor: | Peter P. Ruvolo, Hagop M. Kantarjian, Elihu H. Estey, Jan A. Burger, Roland B. Walter, Stefan Faderl, Michael Andreeff, Zhihong Zeng, Keith A. Baggerly, Gautam Borthakur, Xuelin Huang, Tapan M. Kadia, Wenbin Liu, Jennie Feliu, Marina Konopleva, Elias Jabbour, Steven M. Kornblau |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Akt/PKB signaling pathway business.industry Phases of clinical research Myeloid leukemia Induction chemotherapy Cancer medicine.disease chemistry.chemical_compound chemistry hemic and lymphatic diseases Internal medicine MK-2206 Immunology medicine Phosphorylation business Protein kinase B |
| Zdroj: | Cancer Research. 73:LB-293 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Outcomes of adults with AML remain unsatisfactory. To explore the role of the AKT signaling pathway in AML, we examined samples from AML patients (pts) utilizing reverse phase protein arrays (RPPAs). High levels of the phosphorylated Ser473 form of AKT were associated with shorter remission (p=0.03) and shorter overall survival (p=0.09) in 92 newly diagnosed AML pats with intermediate-risk cytogenetics undergoing induction chemotherapy, identifying AKT as rational drug target. We studied the effects of MK-2206, an investigative oral, highly specific allosteric inhibitor of the 3 isoforms of human AKT, in human AML. MK-2206 dephosphorylated AKT and inhibited growth of AML cell lines and primary AML blasts at low-micromolar concentrations. We then conducted a phase 2 trial of MK-2206 (200 mg once weekly) in adult pats who had failed 1 other therapy for persistent AML or relapsed after a prior CR Citation Format: Marina Y. Konopleva, Roland B. Walter, Stefan Faderl, Elias Jabbour, Zhihong Zeng, Gautam Borthakur, Peter Ruvolo, Xuelin Huang, Tapan Kadia, Jennie Feliu, Jan A. Burger, Michael Andreeff, Wenbin Liu, Steven M. Kornblau, Keith Baggerly, Elihu Estey, Hagop Kantarjian. Phase II study of the oral AKT inhibitor, MK-2206, for acute myeloid leukemia (AML) in second relapse. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-293. doi:10.1158/1538-7445.AM2013-LB-293 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|