Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2014
Preclinical and early clinical evaluation of the oral AKT inhibitor, MK-2206, for the treatment of acute myelogenous leukemia.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 83 citations in OpenAlex.
- Oral MEK 1/2 Inhibitor Trametinib in Combination With AKT Inhibitor GSK2141795 in Patients With Acute Myeloid Leukemia With RAS Mutations: A Phase II Study.Clinical lymphoma, myeloma & leukemia · 2019Trial
- Phase II study of an AKT inhibitor MK2206 in patients with relapsed or refractory lymphoma.British journal of haematology · 2015Trial
- Review
- Enhancing Chemotherapeutic Efficacy in Lung Cancer Cells Through Synergistic Targeting of the PI3K/AKT Pathway with Small Molecule Inhibitors.International journal of molecular sciences · 2025Article
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- Uncoupling of Akt and mTOR signaling drives resistance to Akt inhibition in PTEN loss prostate cancers.Science advances · 2025Article
- The Interlinking Metabolic Association between Type 2 Diabetes Mellitus and Cancer: Molecular Mechanisms and Therapeutic Insights.Diagnostics (Basel, Switzerland) · 2024Review
- Caspase-2 is essential for proliferation and self-renewal of nucleophosmin-mutated acute myeloid leukemia.Science advances · 2024Article
- Article
- Innovations in conditioning and post-transplant maintenance in AML: genomically informed revelations on the graft-versus-leukemia effect.Frontiers in immunology · 2024Review
- The roles of phosphorylation of signaling proteins in the prognosis of acute myeloid leukemia.Pathology oncology research : POR · 2024Article
- Review
- Combined BCL-2 and PI3K/AKT Pathway Inhibition inInternational journal of molecular sciences · 2023Article
- A novel small molecule, CU05-1189, targeting the pleckstrin homology domain of PDK1 suppresses VEGF-mediated angiogenesis and tumor growth by blocking the Akt signaling pathway.Frontiers in pharmacology · 2023Article
- AKT inhibition interferes with the expression of immune checkpoint proteins and increases NK-induced killing of HL60-AML cells.Einstein (Sao Paulo, Brazil) · 2023Article
- Article
- Phosphoproteomics of primary AML patient samples reveals rationale for AKT combination therapy and p53 context to overcome selinexor resistance.Cell reports · 2022Article
- Emerging Targeted Therapy for Specific Genomic Abnormalities in Acute Myeloid Leukemia.International journal of molecular sciences · 2022Review
- PI3K Targeting in Non-solid Cancer.Current topics in microbiology and immunology · 2022Review
- Targeting PI3K/Akt signal transduction for cancer therapy.Signal transduction and targeted therapy · 2021Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
Abstract
purposeRecent studies suggested that AKT activation might confer poor prognosis in acute myelogenous 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 II 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).
resultsIn preclinical studies, MK-2206 dose-dependently inhibited growth and induced apoptosis in AML cell lines and primary AML blasts. We then treated 19 patients with MK-2206 but, among 18 evaluable participants, observed only 1 (95% confidence interval, 0%-17%) response (complete remission with incomplete platelet count recovery), leading to early study termination. The most common grade 3/4 drug-related toxicity was a pruritic rash in 6 of 18 patients. Nevertheless, despite the use of MK-2206 at maximum tolerated doses, RPPA analyses indicated only modest decreases in Ser473 AKT (median 28%; range, 12%-45%) and limited inhibition of downstream targets.
conclusionsAlthough preclinical activity of MK-2206 can be demonstrated, this inhibitor has insufficient clinical antileukemia activity when given alone at tolerated doses, and alternative approaches to block AKT signaling should be explored.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.