ArticleEndocrine-related cancer2013
Targeting mTOR in RET mutant medullary and differentiated thyroid cancer cells.
Article in Endocrine-related cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- The Role of Activation of PI3K/AKT/mTOR and RAF/MEK/ERK Pathways in Aggressive Pituitary Adenomas-New Potential Therapeutic Approach-A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Dual targeting of RET and SRC synergizes in RET fusion-positive cancer cells.Molecular oncology · 2026Article
- Selpercatinib mitigates microglia-mediated neuroinflammation by inhibiting RET signaling and NLRP3 inflammasome activation.Frontiers in immunology · 2026Article
- Activation of the AKT-mTOR pathway confers selpercatinib resistance in thyroid cancer cells harboring theBiochemistry and biophysics reports · 2025Article
- Multiple ctDNA- based biomarkers predict benefit from selective RET Inhibition in non-small cell lung cancer patients: exploratory analysis of a prospective study.Biomarker research · 2025Article
- Systemic Therapies for Advanced Medullary Thyroid Carcinoma.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2025Review
- Improving susceptibility of neuroendocrine tumors to radionuclide therapies: personalized approaches towards complementary treatments.Theranostics · 2024Review
- REThinking the role of the RET oncogene in breast cancer.Frontiers in oncology · 2024Review
- Medullary Thyroid Cancer: Updates and Challenges.Endocrine reviews · 2023Article
- From Circulating Tumor Cells to Mirna: New Challenges in the Diagnosis and Prognosis of Medullary Thyroid Cancer.Cancers · 2023Review
- ZD6474 attenuates TGF-β1-induced fibrosis in human Tenon fibroblasts and inhibits neovascularization via AKT-mTOR signaling pathway.International ophthalmology · 2023Article
- RET signaling in breast cancer therapeutic resistance and metastasis.Breast cancer research : BCR · 2023Review
- Clinical Implications of mTOR Expression in Papillary Thyroid Cancer-A Systematic Review.Cancers · 2023Review
- AST-487 Inhibits RET Kinase Driven TERT Expression in Bladder Cancer.International journal of molecular sciences · 2022Article
- Metastatic medullary thyroid carcinoma: a new way forward.Endocrine-related cancer · 2022Review
- RET kinase inhibitors forTherapeutic advances in medical oncology · 2022Review
- Article
- Multikinase inhibitors in thyroid cancer: timing of targeted therapy.Nature reviews. Endocrinology · 2021Review
- Advances in Targeting RET-Dependent Cancers.Cancer discovery · 2020Review
- Transcriptome Characterization of Matched Primary Breast and Brain Metastatic Tumors to Detect Novel Actionable Targets.Journal of the National Cancer Institute · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Inhibitors of RET, a tyrosine kinase receptor encoded by a gene that is frequently mutated in medullary thyroid cancer, have emerged as promising novel therapies for the disease. Rapalogs and other mammalian target of rapamycin (mTOR) inhibitors are effective agents in patients with gastroenteropancreatic neuroendocrine tumors, which share lineage properties with medullary thyroid carcinomas. The objective of this study was to investigate the contribution of mTOR activity to RET-induced signaling and cell growth and to establish whether growth suppression is enhanced by co-targeting RET and mTOR kinase activities. Treatment of the RET mutant cell lines TT, TPC-1, and MZ-CRC-1 with AST487, a RET kinase inhibitor, suppressed growth and showed profound and sustained inhibition of mTOR signaling, which was recapitulated by siRNA-mediated RET knockdown. Inhibition of mTOR with INK128, a dual mTORC1 and mTORC2 kinase inhibitor, also resulted in marked growth suppression to levels similar to those seen with RET blockade. Moreover, combined treatment with AST487 and INK128 at low concentrations suppressed growth and induced apoptosis. These data establish mTOR as a key mediator of RET-mediated cell growth in thyroid cancer cells and provide a rationale for combinatorial treatments in thyroid cancers with oncogenic RET mutations.
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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.