ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Sorafenib and Quinacrine Target Anti-Apoptotic Protein MCL1: A Poor Prognostic Marker in Anaplastic Thyroid Cancer (ATC).
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2021Guideline
- [Inhibitory effect of lonafarnib on anaplastic thyroid carcinoma cells and xenograft tumor growth in nude mice].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Article
- Osteopontin-4 (OPN-4) Suppresses Tumor Progression Features Whilst Sensitizing c643 Anaplastic Thyroid Cells to Sorafenib.Biomedicines · 2026Article
- Anaplastic thyroid cancer: Genetic roles, targeted therapy, and immunotherapy.Genes & diseases · 2025Review
- Quinacrine Inhibits Hepatocellular Carcinoma Growth and Enhances the Anti-HCC Effects of Lenvatinib.Anti-cancer agents in medicinal chemistry · 2025Article
- NF-κB in Thyroid Cancer: An Update.International journal of molecular sciences · 2024Review
- Pharmacology Progresses and Applications of Chloroquine in Cancer Therapy.International journal of nanomedicine · 2024Review
- Calf Thymus DNA Exposed to Quinacrine at Physiological Temperatures and pH Acquires Immunogenicity: A Threat for Long Term Quinacrine Therapy.Indian journal of clinical biochemistry : IJCB · 2022Article
- Mitochondrial Metabolism in Melanoma.Cells · 2021Review
- Article
- Targeting tumor hypoxia and mitochondrial metabolism with anti-parasitic drugs to improve radiation response in high-grade gliomas.Journal of experimental & clinical cancer research : CR · 2020Review
- Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses.Cells · 2020Review
- Preclinical and clinical combination therapies in the treatment of anaplastic thyroid cancer.Medical oncology (Northwood, London, England) · 2020Review
- Repositioning Quinacrine Toward Treatment of Ovarian Cancer by Rational Combination With TRAIL.Frontiers in oncology · 2020Article
- Synergy of GSK-J4 With Doxorubicin in KRAS-Mutant Anaplastic Thyroid Cancer.Frontiers in pharmacology · 2020Article
- Quinacrine-Mediated Inhibition of Nrf2 Reverses Hypoxia-Induced 5-Fluorouracil Resistance in Colorectal Cancer.International journal of molecular sciences · 2019Article
- Repurposed quinacrine synergizes with cisplatin, reducing the effective dose required for treatment of head and neck squamous cell carcinoma.Oncotarget · 2019Article
- Therapeutic advances in anaplastic thyroid cancer: a current perspective.Molecular cancer · 2018Review
- Inhibition of Mitochondrial Matrix Chaperones and Antiapoptotic Bcl-2 Family Proteins Empower Antitumor Therapeutic Responses.Cancer research · 2017Article
- The Role of Angiogenesis in Cancer Treatment.Biomedicines · 2017Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
PURPOSE AND EXPERIMENTAL
designAnaplastic thyroid cancer (ATC) comprises approximately 2% of all thyroid cancers, and its median survival rate remains poor. It is responsible for more than one third of thyroid cancer-related deaths. ATC is frequently resistant to conventional therapy, and NFκB signaling has been proposed to be a feature of the disease. We aimed to assess the activity of the antimalaria drug quinacrine known to target NFκB signaling in combination with the clinically relevant kinase inhibitor sorafenib in ATC cells. The presence of NFκB-p65/RELA and its target MCL1 was demonstrated in ATC by meta-data gene set enrichment analysis and IHC. We assessed the responses of a panel of human ATC cell lines to quinacrine and sorafenib in vitro and in vivo
resultsWe detected increased expression of NFκB-p65/RELA and MCL1 in the nucleus of a subset of ATC compared with non-neoplastic thyroid. ATC cells were found to respond with additive/synergistic tumor cell killing to the combination of sorafenib plus quinacrine in vitro, and the drug combination improves survival of immunodeficient mice injected orthotopically with ATC cells as compared with mice administered either compound alone or doxorubicin. We also demonstrate that the combination of sorafenib and quinacrine is well tolerated in mice. At the molecular level, quinacrine and sorafenib inhibited expression of prosurvival MCL1, pSTAT3, and dampened NFκB signaling.
conclusionsThe combination of quinacrine and sorafenib targets emerging molecular hallmarks of ATC and shows promising results in clinically relevant models for the disease. Further testing of sorafenib plus quinacrine can be conducted in ATC patients. Clin Cancer Res; 22(24); 6192-203. ©2016 AACR.
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