ArticleOncogenesis2018
Src-mediated regulation of the PI3K pathway in advanced papillary and anaplastic thyroid cancer.
Article in Oncogenesis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
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- Glucose Metabolic Reprogramming in Thyroid Cancer: Underlying Molecular Mechanisms and Links to Progression and Treatment.Current medical science · 2026Review
- Mechanical regulation of metabolism, epigenetics, and their interplay.npj biomedical innovations · 2026Review
- Intersection Between Local Anesthetics and Cancer Biology: What Now? Where Are We Going?Advanced biology · 2025Review
- Targeting Src tyrosine kinase to enhance radioiodide uptake in breast cancer.Endocrine-related cancer · 2025Article
- Anaplastic thyroid cancer: Genetic roles, targeted therapy, and immunotherapy.Genes & diseases · 2025Review
- Menopause-induced 17β-estradiol and progesterone loss increases senescence markers, matrix disassembly and degeneration in mouse cartilage.Nature aging · 2025Article
- Tyrosine Protein Kinase SYK-Related Gene Signature in Baseline Immune Cells Associated with Adjuvant Immunotherapy-Induced Immune-Related Adverse Events in Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
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- Effect of 660-nm LED photobiomodulation on the proliferation and chondrogenesis of meniscus-derived stem cells (MeSCs).Scientific reports · 2024Article
- Non-Receptor Tyrosine Kinases: Their Structure and Mechanistic Role in Tumor Progression and Resistance.Cancers · 2024Review
- TPX2 overexpression promotes sensitivity to dasatinib in breast cancer by activating YAP transcriptional signaling.Molecular oncology · 2024Article
- Understanding the Role of Connexins in Hepatocellular Carcinoma: Molecular and Prognostic Implications.Cancers · 2024Review
- Logic-based mechanistic machine learning on high-content images reveals how drugs differentially regulate cardiac fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Logic-based mechanistic machine learning on high-content images reveals how drugs differentially regulate cardiac fibroblasts.bioRxiv : the preprint server for biology · 2023Article
- AKT-independent signaling in PIK3CA-mutant thyroid cancer mediates resistance to dual SRC and MEK1/2 inhibition.Medical oncology (Northwood, London, England) · 2023Article
- Article
- Pan-cancer Analysis Reveals SRC May Link Lipid Metabolism and Macrophages.Iranian journal of biotechnology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Advanced stages of papillary and anaplastic thyroid cancer continue to be plagued by a dismal prognosis, which is a result of limited effective therapies for these cancers. Due to the high proportion of thyroid cancers harboring mutations in the MAPK pathway, the MAPK pathway has become a focal point for therapeutic intervention in thyroid cancer. Unfortunately, unlike melanoma, a similar responsiveness to MAPK pathway inhibition has yet to be observed in thyroid cancer patients. To address this issue, we have focused on targeting the non-receptor tyrosine kinase, Src, and we and others have demonstrated that targeting Src results in inhibition of growth, invasion, and migration both in vitro and in vivo, which can be enhanced through the combined inhibition of Src and the MAPK pathway. Therefore, we examined the efficacy of the combination therapy across a panel of thyroid cancer cell lines representing common oncogenic drivers (BRAF, RAS, and PIK3CA). Interestingly, combined inhibition of Src and the MAPK pathway overcomes intrinsic dasatinib resistance in cell lines where both the MAPK and PI3K pathways are inhibited, which we show is likely due to the regulation of the PI3K pathway by Src in these responsive cells. Interestingly, we have mapped downstream phosphorylation of rpS6 as a key biomarker of response, and cells that maintain rpS6 phosphorylation likely represent drug tolerant persisters. Altogether, the combined inhibition of Src and the MAPK pathway holds great promise for improving the overall survival of advanced thyroid cancer patients with BRAF and RAS mutations, and activation of the PI3K pathway and rpS6 phosphorylation represent important biomarkers of response for patients treated with this therapy.
Identifiers
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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.