Preclinical and Early Clinical Evaluation of the Oral AKT Inhibitor, MK-2206, for the Treatment of Acute Myeloid Leukemia.

Publication Type:

Journal Article

Source:

Clinical cancer research : an official journal of the American Association for Cancer Research, Volume 20, Issue 8, p.2226-35 (2014)

Keywords:

2014, Center-Authored Paper, Clinical Research Division, Flow Cytometry Core Facility, March 2014, Research Trials Office Core Facility - Biostatistics Service, Specimen Processing Core Facility

Abstract:

Recent studies suggested that AKT activation might confer poor prognosis in acute myeloid leukemia (AML), providing the rationale for therapeutic targeting of this signaling pathway. We therefore explored the preclinical and clinical anti-AML activity of an oral AKT inhibitor, MK-2206. Experimental Methods: We first studied the effects of MK-2206 in human AML cell lines and primary AML specimens in vitro. Subsequently, we conducted a phase 2 trial of MK-2206 (200 mg weekly) in adults requiring second salvage therapy for relapsed/refractory AML, and assessed target inhibition via reverse phase protein array (RPPA).