Trial reportInvestigational new drugs2015
Biomarker-driven phase 2 study of MK-2206 and selumetinib (AZD6244, ARRY-142886) in patients with colorectal cancer.
Trial report in Investigational new drugs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
78 citing papers in PubMed, 135 citations in OpenAlex.
- Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.Nature medicine · 2025Trial
- A Phase I Study of Dinaciclib in Combination With MK-2206 in Patients With Advanced Pancreatic Cancer.Clinical and translational science · 2020Trial
- Effect of Selumetinib and MK-2206 vs Oxaliplatin and Fluorouracil in Patients With Metastatic Pancreatic Cancer After Prior Therapy: SWOG S1115 Study Randomized Clinical Trial.JAMA oncology · 2017Trial
- Review
- EIF4A3/circPTGR1/miR-4725-5p positive- feedback loop promotes colorectal cancer progression via FAK/AKT signaling pathway.Molecular cancer · 2026Article
- Research progress of small molecule protein kinase inhibitors (SMKIs) in the treatment of colorectal cancer: mechanism, application, and future prospects.Frontiers in pharmacology · 2026Review
- Targeting KRAS in colorectal cancer (Review).Molecular and clinical oncology · 2025Review
- A Phase Ia/b study of MEK1/2 inhibitor binimetinib with MET inhibitor crizotinib in patients with RAS mutant advanced colorectal cancer (MErCuRIC).BMC cancer · 2025Article
- Secreted Cytokines From Inflammatory Macrophages Modulate Sex Differences in Valvular Interstitial Cells on Hydrogel Biomaterials.Journal of biomedical materials research. Part A · 2025Article
- KRAS mutants confer platinum resistance by regulating ALKBH5 posttranslational modifications in lung cancer.The Journal of clinical investigation · 2025Article
- Dual Inhibition of PI3 Kinase and MAP Kinase Signaling Pathways in Intrahepatic Cholangiocellular Carcinoma Cell Lines Leads to Proliferation Arrest but Not Apoptosis.Current issues in molecular biology · 2024Article
- PI3K/Akt/mTOR Signaling Pathway as a Target for Colorectal Cancer Treatment.International journal of molecular sciences · 2024Review
- BRAF - a tumour-agnostic drug target with lineage-specific dependencies.Nature reviews. Clinical oncology · 2024Review
- Enhancing efficacy of the MEK inhibitor trametinib with paclitaxel inTherapeutic advances in medical oncology · 2024Article
- Colorectal Cancer Stem Cells and Targeted Agents.Pharmaceutics · 2023Review
- The current landscape of using direct inhibitors to target KRASExperimental hematology & oncology · 2023Review
- Unveiling the genetic and epigenetic landscape of colorectal cancer: new insights into pathogenic pathways.Medical oncology (Northwood, London, England) · 2023Review
- Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer.Molecular cancer therapeutics · 2023Article
- Selumetinib: a selective MEK1 inhibitor for solid tumor treatment.Clinical and experimental medicine · 2023Review
- The Therapeutic Landscape forCancers · 2023Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
purposePI3K/AKT/mTOR and RAS/RAF/MEK pathways are frequently dysregulated in colorectal cancer (CRC). We conducted a biomarker-driven trial of the combination of MK-2206, an allosteric AKT 1/2/3 inhibitor, and selumetinib, a MEK 1/2 inhibitor, in patients with CRC to evaluate inhibition of phosphorylated ERK (pERK) and AKT (pAKT) in paired tumor biopsies. PATIENTS AND
methodsAdult patients with advanced CRC were enrolled in successive cohorts stratified by KRAS mutation status. Initially, 12 patients received oral MK-2206 90 mg weekly with oral selumetinib 75 mg daily in 28-day cycles. Following an interim analysis, the doses of MK-2206 and selumetinib were increased to 135 mg weekly and 100 mg daily, respectively. Paired tumor biopsies were evaluated for target modulation.
resultsCommon toxicities were gastrointestinal, hepatic, dermatologic, and hematologic. Of 21 patients enrolled, there were no objective responses. Target modulation did not achieve the pre-specified criteria of dual 70 % inhibition of pERK and pAKT levels in paired tumor biopsies.
conclusionDespite strong scientific rationale and preclinical data, clinical activity was not observed. The desired level of target inhibition was not achieved. Overlapping toxicities limited the ability to dose escalate to achieve exposures likely needed for clinical activity, highlighting the challenges in developing optimal combinations of targeted agents.
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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.