ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers, 2 of them syntheses that pooled it.
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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
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- A comprehensive overview of the molecular features and therapeutic targets in BRAFClinical and translational medicine · 2024Pooled it
- Pathogenetic mechanisms of focal cortical dysplasia.Epilepsia · 2014Pooled it
- Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- Mouse models in colon cancer, inferences, and implications.iScience · 2023Review
- Immune checkpoint blockade therapy for BRAF mutant metastatic colorectal cancer: the efficacy, new strategies, and potential biomarkers.Discover oncology · 2023Review
- The Sphingosine Kinase 2 Inhibitor ABC294640 Restores the Sensitivity of BRAFV600E Mutant Colon Cancer Cells to Vemurafenib by Reducing AKT-Mediated Expression of Nucleophosmin and Translationally-Controlled Tumour Protein.International journal of molecular sciences · 2021Article
- Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib.International journal of molecular sciences · 2021Article
- Targeted drug delivery strategies for precision medicines.Nature reviews. Materials · 2021Article
- Article
- Integrin-Src-YAP1 signaling mediates the melanoma acquired resistance to MAPK and PI3K/mTOR dual targeted therapy.Molecular biomedicine · 2020Article
- Contemporary treatment approaches for metastatic colorectal cancer driven byWorld journal of gastrointestinal oncology · 2020Review
- Mouse models of colorectal cancer: Past, present and future perspectives.World journal of gastroenterology · 2020Review
- Advances in Modeling the Immune Microenvironment of Colorectal Cancer.Frontiers in immunology · 2020Review
- Article
- mTOR mediates a mechanism of resistance to chemotherapy and defines a rational combination strategy to treat KRAS-mutant lung cancer.Oncogene · 2019Article
- Clinicopathologic features and treatment efficacy of Chinese patients with BRAF-mutated metastatic colorectal cancer: a retrospective observational study.Chinese journal of cancer · 2017Observational
- Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer.Journal of visualized experiments : JoVE · 2017Article
- New frontiers in the treatment of colorectal cancer: Autophagy and the unfolded protein response as promising targets.Autophagy · 2017Review
- PKM2 is not required for colon cancer initiated by APC loss.Cancer & metabolism · 2017Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeBRAF(V600E) mutations are associated with poor clinical prognosis in colorectal cancer (CRC). Although selective BRAF inhibitors are effective for treatment of melanoma, comparable efforts in CRC have been disappointing. Here, we investigated potential mechanisms underlying this resistance to BRAF inhibitors in BRAF(V600E) CRC. EXPERIMENTAL
designWe examined phosphoinositide 3-kinase (PI3K)/mTOR signaling in BRAF(V600E) CRC cell lines after BRAF inhibition and cell viability and apoptosis after combined BRAF and PI3K/mTOR inhibition. We assessed the efficacy of in vivo combination treatment using a novel genetically engineered mouse model (GEMM) for BRAF(V600E) CRC.
resultsWestern blot analysis revealed sustained PI3K/mTOR signaling upon BRAF inhibition. Our BRAF(V600E) GEMM presented with sessile serrated adenomas/polyps, as seen in humans. Combination treatment in vivo resulted in induction of apoptosis and tumor regression.
conclusionsWe have established a novel GEMM to interrogate BRAF(V600E) CRC biology and identify more efficacious treatment strategies. Combination BRAF and PI3K/mTOR inhibitor treatment should be explored in clinical trials.
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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.