ReviewInternational journal of molecular sciences2015
Dual Inhibition of MEK and PI3K Pathway in KRAS and BRAF Mutated Colorectal Cancers.
Review in International journal of molecular sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 5 of them syntheses that pooled it.
What it found
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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
79 citing papers in PubMed, 5 syntheses or guidelines pooled it, 120 citations in OpenAlex.
- The safety and efficacy of binimetinib for lung cancer: a systematic review.BMC pulmonary medicine · 2024Pooled it
- A comprehensive overview of the molecular features and therapeutic targets in BRAFClinical and translational medicine · 2024Pooled it
- Genomic Heterogeneity and Exceptional Response to Dual Pathway Inhibition in Anaplastic Thyroid Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Pooled it
- Molecular Biomarkers for the Evaluation of Colorectal Cancer.American journal of clinical pathology · 2017Guideline
- Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology.The Journal of molecular diagnostics : JMD · 2017Guideline
- Oncogenic RAS as an adaptive signaling ecosystem: context-dependent vulnerabilities and resistance-informed therapeutic design.Experimental hematology & oncology · 2026Review
- Overcoming Resistance to Anti-EGFR Therapies: Mechanisms of Cetuximab and Panitumumab Resistance and Emerging Combination Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- RHEBL1 expression is activated by the Oct4-Sox2 complex in oral squamous cell carcinoma.Functional & integrative genomics · 2026Article
- Article
- A Further Case for Targeting PRMT5 and the ERK1/2 and PI3K Pathways in CRC.International journal of molecular sciences · 2025Article
- Rapamycin suppresses small bowel adenocarcinoma HUTU 80 cells proliferation by inhibiting hypoxia-inducible factor-1α mediated metabolic reprogramming.World journal of gastrointestinal oncology · 2025Article
- The multifaceted roles of ZIC genes in cancer: from development regulators to cancer modulators.Discover oncology · 2025Review
- Integrated In Silico and Experimental Validation of Antrocin as a Plant-Derived Multi-Target Therapeutic for BRAF/MEK/PI3K-Driven Colorectal Cancer.International journal of molecular sciences · 2025Article
- Spike-in enhanced phosphoproteomics uncovers synergistic signaling responses to MEK inhibition in colon cancer cells.Nature communications · 2025Article
- Mechanisms of KRAS inhibitor resistance in KRAS-mutant colorectal cancer harboring Her2 amplification and aberrant KRAS localization.NPJ precision oncology · 2025Article
- Noninvasive Therapeutic Monitoring of Circulating Tumor DNA in BRAF-Mutant Metastatic Colon Cancer Using Droplet Digital PCR, Next-Generation Sequencing, and Fragmentomics.Case reports in oncological medicine · 2025Article
- An overview of recent advancements in small molecules suppression of oncogenic signaling of K-RAS: an updated review.Molecular diversity · 2024Review
- Metabolic Response to Small Molecule Therapy in Colorectal Cancer Tracked with Raman Spectroscopy and Metabolomics.Angewandte Chemie (International ed. in English) · 2024Article
- KRAS Mutation Subtypes and Their Association with Other Driver Mutations in Oncogenic Pathways.Cells · 2024Review
- Concurrent inhibition of pBADS99 synergistically improves MEK inhibitor efficacy in KRASCell death & disease · 2024Article
19 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
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. Genetic mutations in the phosphatidylinositol-3 kinase (PI3K) and the mitogen activated protein kinase (MAPK) pathways are frequently implicated in CRC. Targeting the downstream substrate MEK in these mutated tumors stands out as a potential target in CRC. Several selective inhibitors of MEK have entered clinical trial evaluation; however, clinical activity with single MEK inhibitors has been rarely observed and acquired resistance seems to be inevitable. Amplification of the driving oncogene KRAS(13D), which increases signaling through the ERK1/2 pathway, upregulation of the noncanonical wingless/calcium signaling pathway (Wnt), and coexisting PIK3CA mutations have all been implicated with resistance against MEK inhibitor therapy in KRAS mutated CRC. The Wnt pathway and amplification of the oncogene have also been associated with resistance to MEK inhibitors in CRCs harboring BRAF mutations. Thus, dual targeted inhibition of MEK and PI3K pathway effectors (mTOR, PI3K, AKT, IGF-1R or PI3K/mTOR inhibitors) presents a potential strategy to overcome resistance to MEK inhibitor therapy. Many clinical trials are underway to evaluate multiple combinations of these pathway inhibitors in solid tumors.
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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.