ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers.
Article 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. It is linked to trial NCT00670488 (A Phase I Dose Escalation Study of Oral MK-2206 in Patients With Locally Advanced or Metastatic Solid Tumors), which is not on this map. Cited by 52 papers.
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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.
A Phase I Dose Escalation Study of Oral MK-2206 in Patients With Locally Advanced or Metastatic Solid Tumors
Who cites it
52 citing papers in PubMed.
- A phase 2 study of MK-2206 in patients with incurable adenoid cystic carcinoma (Alliance A091104).Cancer · 2024Trial
- A Phase I Study of Dinaciclib in Combination With MK-2206 in Patients With Advanced Pancreatic Cancer.Clinical and translational science · 2020Trial
- Phase II, 2-stage, 2-arm, PIK3CA mutation stratified trial of MK-2206 in recurrent endometrial cancer.International journal of cancer · 2020Trial
- Metabolomic changes of the multi (-AGC-) kinase inhibitor AT13148 in cells, mice and patients are associated with NOS regulation.Metabolomics : Official journal of the Metabolomic Society · 2020Trial
- Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation.Breast cancer research : BCR · 2019Trial
- Pre-surgical trial of the AKT inhibitor MK-2206 in patients with operable invasive breast cancer: a New York Cancer Consortium trial.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Trial
- A Phase II Trial of Neoadjuvant MK-2206, an AKT Inhibitor, with Anastrozole in Clinical Stage II or IIIClinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- A randomized phase 2 study of MK-2206 versus everolimus in refractory renal cell carcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- Novel pharmacodynamic biomarkers for MYCN protein and PI3K/AKT/mTOR pathway signaling in children with neuroblastoma.Molecular oncology · 2016Trial
- Multicenter phase II study of the AKT inhibitor MK-2206 in recurrent or metastatic nasopharyngeal carcinoma from patients in the mayo phase II consortium and the cancer therapeutics research group (MC1079).Investigational new drugs · 2015Trial
- PTEN loss and ERBB2/ERBB3-mediated AKT reactivation drive resistance to MET inhibition in MET-amplified hepatocellular carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- The Precision-Guided Use of PI3K Pathway Inhibitors for the Treatment of Solid Malignancies.Biomedicines · 2025Review
- Theoretical investigation of AKT1 mutations in breast cancer: a computational approach to structural and functional insights.Journal of computer-aided molecular design · 2025Article
- Inhibition of AKT enhances chemotherapy efficacy and synergistically interacts with targeting of the Inhibitor of apoptosis proteins in oesophageal adenocarcinoma.Scientific reports · 2024Article
- AXL-TBK1 driven AKT3 activation promotes metastasis.Science signaling · 2024Article
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- Medication-Induced Hyperglycemia and Diabetes Mellitus: A Review of Current Literature and Practical Management Strategies.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2024Review
- Severe Lactic Acidosis Complicated by Insulin-Resistant Hyperosmolar Hyperglycemic Syndrome in a Patient With Metastatic Breast Cancer Undergoing AKT-Inhibitor Therapy.JCO precision oncology · 2022Article
- Role of PI3K/Akt/mTOR pathway in mediating endocrine resistance: concept to clinic.Exploration of targeted anti-tumor therapy · 2022Review
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
purposeMultiple cancers harbor genetic aberrations that impact AKT signaling. MK-2206 is a potent pan-AKT inhibitor with a maximum tolerated dose (MTD) previously established at 60 mg on alternate days (QOD). Due to a long half-life (60-80 hours), a weekly (QW) MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. EXPERIMENTAL
designPatients with advanced cancers were enrolled in a QW dose-escalation phase I study to investigate the safety and pharmacokinetic-pharmacodynamic profiles of tumor and platelet-rich plasma (PRP). The QOD MTD of MK-2206 was also assessed in patients with ovarian and castration-resistant prostate cancers and patients with advanced cancers undergoing multiparametric functional magnetic resonance imaging (MRI) studies, including dynamic contrast-enhanced MRI, diffusion-weighted imaging, magnetic resonance spectroscopy, and intrinsic susceptibility-weighted MRI.
resultsA total of 71 patients were enrolled; 38 patients had 60 mg MK-2206 QOD, whereas 33 received MK-2206 at 90, 135, 150, 200, 250, and 300 mg QW. The QW MK-2206 MTD was established at 200 mg following dose-limiting rash at 250 and 300 mg. QW dosing appeared to be similarly tolerated to QOD, with toxicities including rash, gastrointestinal symptoms, fatigue, and hyperglycemia. Significant AKT pathway blockade was observed with both continuous QOD and intermittent QW dosing of MK-2206 in serially obtained tumor and PRP specimens. The functional imaging studies demonstrated that complex multiparametric MRI protocols may be effectively implemented in a phase I trial.
conclusionsTreatment with MK-2206 safely results in significant AKT pathway blockade in QOD and QW schedules. The intermittent dose of 200 mg QW is currently used in phase II MK-2206 monotherapy and combination studies (NCT00670488).
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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.