ArticleCell death & disease2014
Blocks to thyroid cancer cell apoptosis can be overcome by inhibition of the MAPK and PI3K/AKT pathways.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- The molecular mechanisms and potential therapeutic implications of the crosstalk between DNA methylation and metabolic reprogramming in thyroid cancer.Cell death discovery · 2026Review
- Can mutation abundance assess the biological behavior of BRAFJournal of translational medicine · 2025Article
- Periplocin induces necroptosis in papillary thyroid carcinoma through DR4 mediated RIPK3 and MLKL signaling.Scientific reports · 2025Article
- Anaplastic thyroid cancer: Genetic roles, targeted therapy, and immunotherapy.Genes & diseases · 2025Review
- miR-331-5p Affects Motility of Thyroid Cancer Cell Lines and Regulates BID Expression.Biomedicines · 2024Article
- Activation of the JAK/STAT Pathway Leads to BRAF Inhibitor Resistance in BRAFV600E Positive Thyroid Carcinoma.Molecular cancer research : MCR · 2023Article
- Nuclear interaction of Arp2/3 complex and BRAFAmerican journal of cancer research · 2022Article
- Synergistic effect of metformin and vemurufenib (PLX4032) as a molecular targeted therapy in anaplastic thyroid cancer: an in vitro study.Molecular biology reports · 2021Article
- FKBP10 functioned as a cancer-promoting factor mediates cell proliferation, invasion, and migration via regulating PI3K signaling pathway in stomach adenocarcinoma.The Kaohsiung journal of medical sciences · 2020Article
- Molecular therapeutics for anaplastic thyroid cancer.Seminars in cancer biology · 2020Article
- VCAM-1 Upregulation Contributes to Insensitivity of Vemurafenib in BRAF-Mutant Thyroid Cancer.Translational oncology · 2020Article
- Vemurafenib may overcome TNF-related apoptosis-inducing ligand (TRAIL) resistance in anaplastic thyroid cancer cells.Endocrine · 2020Article
- Synergistic repression of thyroid hyperplasia by cyclin C and Pten.Journal of cell science · 2019Article
- Inhibition of Nrf2 promotes the antitumor effect of Pinelliae rhizome in papillary thyroid cancer.Journal of cellular physiology · 2019Article
- Establishment and Characterization of Four Novel Thyroid Cancer Cell Lines and PDX Models Expressing the RET/PTC1 Rearrangement, BRAFV600E, or RASQ61R as Drivers.Molecular cancer research : MCR · 2019Article
- Therapeutic advances in anaplastic thyroid cancer: a current perspective.Molecular cancer · 2018Review
- CRLF1 promotes malignant phenotypes of papillary thyroid carcinoma by activating the MAPK/ERK and PI3K/AKT pathways.Cell death & disease · 2018Article
- Src-mediated regulation of the PI3K pathway in advanced papillary and anaplastic thyroid cancer.Oncogenesis · 2018Article
- The Chinese herbOncology letters · 2017Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Current treatment for recurrent and aggressive/anaplastic thyroid cancers is ineffective. Novel targeted therapies aimed at the inhibition of the mutated oncoprotein BRAF(V600E) have shown promise in vivo and in vitro but do not result in cellular apoptosis. TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a tumor-selective manner by activating the extrinsic apoptotic pathway. Here, we show that a TRAIL-R2 agonist antibody, lexatumumab, induces apoptosis effectively in some thyroid cancer cell lines (HTh-7, TPC-1 and BCPAP), while more aggressive anaplastic cell lines (8505c and SW1736) show resistance. Treatment of the most resistant cell line, 8505c, using lexatumumab in combination with the BRAF(V600E) inhibitor, PLX4720, and the PI3K inhibitor, LY294002, (triple-drug combination) sensitizes the cells by triggering both the extrinsic and intrinsic apoptotic pathways in vitro as well as 8505c orthotopic thyroid tumors in vivo. A decrease in anti-apoptotic proteins, pAkt, Bcl-xL, Mcl-1 and c-FLIP, coupled with an increase in the activator proteins, Bax and Bim, results in an increase in the Bax to Bcl-xL ratio that appears to be critical for sensitization and subsequent apoptosis of these resistant cells. Our results suggest that targeting the death receptor pathway in thyroid cancer can be a promising strategy for inducing apoptosis in thyroid cancer cells, although combination with other kinase inhibitors may be needed in some of the more aggressive tumors initially resistant to apoptosis.
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