ArticleOncotarget2016
Efficacy of the combination of MEK and CDK4/6 inhibitors in vitro and in vivo in KRAS mutant colorectal cancer models.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis 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
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- Pooled it
- Phase II Single-Arm Study of Palbociclib and Cetuximab Rechallenge in Patients with KRAS/NRAS/BRAF Wild-Type Colorectal Cancer.The oncologist · 2022Trial
- Review
- Co-targeting CDK4/6 and MEK reverses mesenchymal transition in therapy-refractory BRAF-altered pediatric high-grade glioma.Journal of experimental & clinical cancer research : CR · 2026Article
- Article
- 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
- Efficacy of CDK4/6 Inhibition in colorectal cancer and the role of p16 expression in predicting drug resistance.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Glutaminase as a metabolic target of choice to counter acquired resistance to Palbociclib by colorectal cancer cells.Oncogene · 2025Article
- Review
- 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
- RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches.Medicina (Kaunas, Lithuania) · 2025Review
- Review
- Effects of combination therapy of a CDK4/6 and MEK inhibitor in diffuse midline glioma preclinical models.PloS one · 2025Article
- Resistance mechanisms and therapeutic strategies of CDK4 and CDK6 kinase targeting in cancer.Nature cancer · 2025Review
- Separable Cell Cycle Arrest and Immune Response Elicited through Pharmacological CDK4/6 and MEK Inhibition in RASmut Disease Models.Molecular cancer therapeutics · 2024Article
- Combinatorial strategies to target RAS-driven cancers.Nature reviews. Cancer · 2024Review
- CDK4/6 inhibition sensitizes MEK inhibition by inhibiting cell cycle and proliferation in pancreatic ductal adenocarcinoma.Scientific reports · 2024Article
- Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of pleural mesotheliomas to CDK4/6 inhibition.Molecular oncology · 2024Article
- Enhancing efficacy of the MEK inhibitor trametinib with paclitaxel inTherapeutic advances in medical oncology · 2024Article
31 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 3 institutions in 1 country.
Funding
Abstract
purposeThough the efficacy of MEK inhibitors is being investigated in KRAS-mutant colorectal cancers (CRC), early clinical trials of MEK inhibitor monotherapy did not reveal significant antitumor activity. Resistance to MEK inhibitor monotherapy developed through a variety of mechanisms converging in ERK reactivation. Since ERK increases cyclin D expression and increases entry into the cell cycle, we hypothesized that the combination of MEK inhibitors and CDK4/6 inhibitors would have synergistic antitumor activity and cause tumor regression in vivo.
resultsThe combination of MEK and CDK4/6 inhibitors synergistically inhibited cancer cell growth in vitro and caused tumor regression in vivo in cell line and patient-derived xenograft models. Combination therapy markedly decreased levels of phosphorylated ribosomal protein S6 both in vitro and in vivo and decreased Ki67 staining in vivo. EXPERIMENTAL
designWe performed in vitro proliferation, colony formation, apoptosis, and senescence assays, and Western blots, on a panel of 11 KRAS mutant CRC cell lines treated with the MEK inhibitor MEK162, the CDK4/6 inhibitor palbociclib, or the combination. We also treated 4 KRAS mutant CRC cell line and patient-derived xenografts with the MEK inhibitor trametinib, the CDK4/6 inhibitor palbociclib, or the combination, and performed immunohistochemical and reverse phase protein array analysis.
conclusionsCombined inhibition of both MEK and CDK4/6 is effective in preclinical models of KRAS mutant CRC and justifies a planned phase II clinical trial in patients with refractory KRAS-mutant CRC.Efficacy of the combination of MEK and CDK4/6 inhibitors in vitro and in vivo in KRAS mutant colorectal cancer models.
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What OpenQuestion holds
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.