ArticleCancer research2022
Targeting RAS Mutant Colorectal Cancer with Dual Inhibition of MEK and CDK4/6.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Trial
- Rewiring the Molecular Interplay of CDK4/6 Inhibitors in Lung Cancer: From Cell Cycle Control to Immune Microenvironment Remodeling.International journal of molecular sciences · 2026Review
- CDK4/6 Inhibitor-Induced Senescence in Cancer: Mechanisms and Therapeutic Implications.Cancers · 2026Review
- From paradox to target: IFN-β hijacks MEK signaling to drive a cell death-evading dormant phenotype in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Filgotinib induces apoptosis in colorectal cancer cells by activating the p53 signaling pathway.Molecular biology reports · 2026Article
- HAUS1-mediated activation of CDK4 transcription enhances proliferation, invasion and migration in hepatocellular carcinoma.Cancer gene therapy · 2026Article
- Harnessing PDX and PDX 2.0: the next-generation paradigm for precision oncology and translational breakthroughs.Molecular cancer · 2026Review
- Differential Preclinical Efficacy of Combined CDK4/6 and MEK Inhibition in Low-Grade Serous Ovarian Carcinoma Based onInternational journal of molecular sciences · 2026Article
- Gastrointestinal toxicity associated with cyclin-dependent kinase 4/6 inhibitors in breast cancer patients: insights from a real-world pharmacovigilance analysis.Frontiers in medicine · 2026Article
- CDK4/6-targeted therapy for gastrointestinal cancers: from resistance mechanisms to immuno-combination strategies guided by biomarkers.Frontiers in immunology · 2026Review
- Cell cycle dysregulation: a central hub in colitis-associated colorectal carcinogenesis.Frontiers in immunology · 2026Review
- Simultaneous targeting of KRAS and CDK4 synergistically induces durable growth arrest in pancreatic cancer cells.Cell death & disease · 2025Article
- Review
- The latest progress of personalized drug screening and therapy research for common clinical tumors through the PDX model platform.Journal of pharmaceutical analysis · 2025Review
- A Phase IB Study of Binimetinib and Palbociclib in Molecularly Selected Advanced Triple-Negative Breast Cancer.Cancer research communications · 2025Article
- Glutaminase as a metabolic target of choice to counter acquired resistance to Palbociclib by colorectal cancer cells.Oncogene · 2025Article
- Review
- Anti-tumor efficacy of RAF/MEK inhibitor VS6766 in KRAS-mutated colorectal cancer cells.Cancer chemotherapy and pharmacology · 2025Article
- KRAS amplification in colorectal cancer: correlations with clinicopathological features and prognosis in patients and prediction of response to targeted therapy.Journal of translational medicine · 2025Article
- Targeting synthetic lethality in colorectal cancer.Chinese medical journal · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
KRAS and NRAS mutations occur in 45% of colorectal cancers, with combined MAPK pathway and CDK4/6 inhibition identified as a potential therapeutic strategy. In the current study, this combinatorial treatment approach was evaluated in a co-clinical trial in patient-derived xenografts (PDX), and safety was established in a clinical trial of binimetinib and palbociclib in patients with metastatic colorectal cancer with RAS mutations. Across 18 PDX models undergoing dual inhibition of MEK and CDK4/6, 60% of tumors regressed, meeting the co-clinical trial primary endpoint. Prolonged duration of response occurred predominantly in TP53 wild-type models. Clinical evaluation of binimetinib and palbociclib in a safety lead-in confirmed safety and provided preliminary evidence of activity. Prolonged treatment in PDX models resulted in feedback activation of receptor tyrosine kinases and acquired resistance, which was reversed with a SHP2 inhibitor. These results highlight the clinical potential of this combination in colorectal cancer, along with the utility of PDX-based co-clinical trial platforms for drug development. SIGNIFICANCE: This co-clinical trial of combined MEK-CDK4/6 inhibition in RAS mutant colorectal cancer demonstrates therapeutic efficacy in patient-derived xenografts and safety in patients, identifies biomarkers of response, and uncovers targetable mechanisms of resistance.
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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.