ArticleOncotarget2017
Combined MEK and Pi3'-kinase inhibition reveals synergy in targeting thyroid cancer in vitro and in vivo.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- ERK Signaling in Thyroid Cancer: Lineage Suppression, Epigenetic Reprogramming, and Theranostic Reversal.Cancers · 2026Review
- Somatic genetic alterations in the development and progression in thyroid tumors of follicular cells.European thyroid journal · 2025Review
- Genomic alterations in thyroid cancer: biological and clinical insights.Nature reviews. Endocrinology · 2024Review
- Mechanistic Insights of Thyroid Cancer Progression.Endocrinology · 2023Review
- Article
- Prospects for Redifferentiating Agents in the Use of Radioactive Iodine Therapy for Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2020Article
- Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses.Cells · 2020Review
- Combined blockade of MEK and PI3KCA as an effective antitumor strategy in HER2 gene amplified human colorectal cancer models.Journal of experimental & clinical cancer research : CR · 2019Article
- Mouse Models for Exploring the Biological Consequences and Clinical Significance ofBiomolecules · 2019Review
- Mouse Models as a Tool for Understanding Progression in BrafEndocrinology and metabolism (Seoul, Korea) · 2019Review
- Inhibition of cisplatin-resistant head and neck squamous cell carcinoma by combination of Afatinib with PD0325901, a MEK inhibitor.American journal of cancer research · 2019Article
- Combined inhibition of MEK and PI3K pathways overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer.Cancer science · 2018Article
- The LAT1 inhibitor JPH203 reduces growth of thyroid carcinoma in a fully immunocompetent mouse model.Journal of experimental & clinical cancer research : CR · 2018Article
- MEK inhibitors induce apoptosis via FoxO3a-dependent PUMA induction in colorectal cancer cells.Oncogenesis · 2018Article
- Src-mediated regulation of the PI3K pathway in advanced papillary and anaplastic thyroid cancer.Oncogenesis · 2018Article
- Development of Fangjiomics for Systems Elucidation of Synergistic Mechanism Underlying Combination Therapy.Computational and structural biotechnology journal · 2018Review
- PIK3CAOncotarget · 2017Article
- Targeting signaling and apoptotic pathways involved in chemotherapeutic drug-resistance of hematopoietic cells.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anaplastic thyroid cancers and radioiodine resistant thyroid cancer are posing a major treat since surgery combined with Iodine131 therapy is ineffective on them. Small-molecule inhibitors are presenting a new hope for patients, but often lead to drug resistance in many cancers. Based on the major mutations found in thyroid cancer, we propose the combination of a MEK inhibitor and a Pi3'-kinase inhibitor in pre-clinical models. We used human thyroid cancer cell lines and genetically engineered double mutant BRAFV600E PIK3CAH1047R mice to evaluate the effect of both inhibitors separately or in combination in terms of proliferation and signaling in vitro; tumor burden, histology, cell death induction and tumor markers expression in vivo. The combination of MEK and Pi'3-kinase inhibition shows a synergistic effect in term of proliferation and apoptosis induction through Survivin down-regulation in vitro. We show for the first time the effects of the combination of a MEK inhibitor and Pi3'-kinase inhibitor in a genetically engineered mouse model of aggressively lethal thyroid cancer. In fine, the two drugs cooperate to promote tumor shrinkage by inducing a proliferation arrest and an elevation of apoptosis in vivo. Moreover, a phenotypic reversion is also observed with a partial restoration of normal thyroid marker transcription, and thyroid cancer marker expression reduction.In conclusion, combination therapy of MEK and Pi3'-kinase inhibition synergizes to target double mutant thyroid cancer in vitro and in vivo. This multidrug approach could readily be translated into clinical practice and bring new perspectives for the treatment of incurable thyroid carcinoma.
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