ArticleCancer research2009
Genetic alterations in the phosphoinositide 3-kinase/Akt signaling pathway confer sensitivity of thyroid cancer cells to therapeutic targeting of Akt and mammalian target of rapamycin.
Article in Cancer research, 2009. 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 48 papers.
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Who cites it
48 citing papers in PubMed, 88 citations in OpenAlex.
- Theranostic and Radionuclide-based Treatment Approaches for Radioiodine-refractory Thyroid Cancer: From Biology to Clinical Application.Molecular imaging and biology · 2026Review
- Drug repositioning in thyroid cancer: from point mutations to gene fusions.Frontiers in oncology · 2024Review
- The potential role of reprogrammed glucose metabolism: an emerging actionable codependent target in thyroid cancer.Journal of translational medicine · 2023Review
- Novel Systemic Treatment Modalities Including Immunotherapy and Molecular Targeted Therapy for Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2022Review
- Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson's disease patients.Scientific reports · 2021Article
- Silencing UHRF1 Inhibits Cell Proliferation and Promotes Cell Apoptosis in Retinoblastoma Via the PI3K/Akt Signalling Pathway.Pathology oncology research : POR · 2020Article
- Papillary Thyroid Carcinoma Variants are Characterized by Co-dysregulation of Immune and Cancer Associated Genes.Cancers · 2019Article
- MAPK- and AKT-activated thyroid cancers are sensitive to group I PAK inhibition.Endocrine-related cancer · 2019Article
- Article
- Peptide P11 suppresses the growth of human thyroid carcinoma by inhibiting the PI3K/AKT/mTOR signaling pathway.Molecular biology reports · 2019Article
- CircRNA circ_0067934 Overexpression Correlates with Poor Prognosis and Promotes Thyroid Carcinoma Progression.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Epigallocatechin-3-gallate inhibits the growth and increases the apoptosis of human thyroid carcinoma cells through suppression of EGFR/RAS/RAF/MEK/ERK signaling pathway.Cancer cell international · 2019Article
- CUX2 functions as an oncogene in papillary thyroid cancer.OncoTargets and therapy · 2019Article
- Targeted next-generation sequencing of cancer-related genes in thyroid carcinoma: A single institution's experience.Oncology letters · 2018Article
- Long Noncoding RNA LINC003121 Inhibits Proliferation and Invasion of Thyroid Cancer Cells by Suppression of the Phosphatidylinositol-3-Kinase (PI3K)/Akt Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Targeting phosphoinositide 3-kinase (PI3K) in head and neck squamous cell carcinoma (HNSCC).Cancers of the head & neck · 2018Review
- Epigenetically upregulated WIPF1 plays a major role in BRAF V600E-promoted papillary thyroid cancer aggressiveness.Oncotarget · 2017Article
- PI3K/AKT Pathway and Its Mediators in Thyroid Carcinomas.Molecular diagnosis & therapy · 2016Review
- REC8 is a novel tumor suppressor gene epigenetically robustly targeted by the PI3K pathway in thyroid cancer.Oncotarget · 2015Article
- Retrospective Study of Sirolimus and Cyclophosphamide in Patients with Advanced Differentiated Thyroid Cancers.Journal of thyroid disorders & therapy · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We investigated the genotype-dependent therapeutic potential of targeting the phosphoinositide 3-kinase (PI3K)/Akt pathway for thyroid cancer. Proliferation of TPC1, Hth7, FTC133, OCUT1, K1, and BCPAP cells that harbored PI3K/Akt-activating genetic alterations was potently inhibited by the Akt inhibitor perifosine, whereas SW1736, Hth74, WRO, KAT18, and TAD2 cells that harbored no genetic alterations had no or only modest responses. Inhibition of Akt phosphorylation by perifosine was seen in these cells. Genetic-dependent apoptosis was induced by perifosine in cells selectively tested. Similarly, potent inhibition of cell proliferation by the mammalian target of rapamycin (mTOR) inhibitor temsirolimus occurred in virtually all the cells harboring genetic alterations, whereas modest inhibition was seen in some of the cells not harboring genetic alterations. Temsirolimus inhibited the phosphorylation of p70S6K, a substrate of mTOR. Knockdown of Akt1/2 or mTOR by shRNA approach inhibited the proliferation and colony formation of FTC133 and OCUT1 cells that harbored genetic alterations in the PI3K/Akt pathway but had no effect on SW1736 and KAT18 cells that did not. Transfection with PIK3CA mutants greatly sensitized SW1736 cells to perifosine and temsirolimus. Growth of xenograft tumors derived from FTC133 cells but not SW1736 cells in nude mice was dramatically inhibited by perifosine. Thus, this work for the first time shows that genetic alterations in the PI3K/Akt pathway confer thyroid cancer cells addiction to this pathway and their sensitivity to inhibition by targeting Akt and mTOR. This genotype-based targeting of the PI3K/Akt pathway using Akt and mTOR inhibitors may offer an effective therapeutic strategy for thyroid cancer and warrants further studies.
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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.