ArticleEndocrine-related cancer2014
Obatoclax overcomes resistance to cell death in aggressive thyroid carcinomas by countering Bcl2a1 and Mcl1 overexpression.
Article in Endocrine-related cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Dedifferentiation and Redifferentiation of Follicular-Cell-Derived Thyroid Carcinoma: Mechanisms and Therapeutic Implications.Biomedicines · 2025Review
- Somatic genetic alterations in the development and progression in thyroid tumors of follicular cells.European thyroid journal · 2025Review
- Development of animal models to study aggressive thyroid cancers.European thyroid journal · 2025Review
- Genomic alterations in thyroid cancer: biological and clinical insights.Nature reviews. Endocrinology · 2024Review
- Construction of an anaplastic thyroid cancer stratification signature to guide immune therapy selection and validation of the pivotal gene HLF throughFrontiers in immunology · 2024Article
- Mechanistic Insights of Thyroid Cancer Progression.Endocrinology · 2023Review
- Additional Oncogenic Alterations in RAS-Driven Differentiated Thyroid Cancers Associate with Worse Clinicopathologic Outcomes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Targeting the IDO-BCL2A1-Cytochrome c Pathway Promotes Apoptosis in Oral Squamous Cell Carcinoma.OncoTargets and therapy · 2021Article
- Discovery and Characterization of 2,5-Substituted Benzoic Acid Dual Inhibitors of the Anti-apoptotic Mcl-1 and Bfl-1 Proteins.Journal of medicinal chemistry · 2020Article
- Review
- MiR-140-5p inhibits cell proliferation and metastasis by regulating MUC1 via BCL2A1/MAPK pathway in triple negative breast cancer.Cell cycle (Georgetown, Tex.) · 2019Article
- Mouse Model of Thyroid Cancer Progression and Dedifferentiation Driven by STRN-ALK Expression and Loss of p53: Evidence for the Existence of Two Types of Poorly Differentiated Carcinoma.Thyroid : official journal of the American Thyroid Association · 2019Article
- SGK1 Is a Critical Component of an AKT-Independent Pathway Essential for PI3K-Mediated Tumor Development and Maintenance.Cancer research · 2017Article
- Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer.Theranostics · 2017Article
- Obatoclax kills anaplastic thyroid cancer cells by inducing lysosome neutralization and necrosis.Oncotarget · 2016Article
- Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers.The Journal of clinical investigation · 2016Article
- The BH3 mimetic drug ABT-737 induces apoptosis and acts synergistically with chemotherapeutic drugs in thyroid carcinoma cells.Cancer cell international · 2016Article
- Article
- Cell death induction by the BH3 mimetic GX15-070 in thyroid carcinoma cells.Journal of experimental & clinical cancer research : CR · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Poorly differentiated tumors of the thyroid gland (PDTC) are generally characterized by a poor prognosis due to their resistance to available therapeutic approaches. The relative rarity of these tumors is a major obstacle to our understanding of the molecular mechanisms leading to tumor aggressiveness and drug resistance, and consequently to the development of novel therapies. By simultaneously activating Kras and deleting p53 (Trp53) in thyroid follicular cells, we have generated a novel mouse model that develops papillary thyroid cancer invariably progressing to PDTC. In several cases, tumors further progress to anaplastic carcinomas. The poorly differentiated tumors are morphologically and functionally similar to their human counterparts and depend on MEK/ERK signaling for proliferation. Using primary carcinomas as well as carcinoma-derived cell lines, we also demonstrate that these tumors are intrinsically resistant to apoptosis due to high levels of expression of the Bcl2 family members, Bcl2a1 (Bcl2a1a) and Mcl1, and can be effectively targeted by Obatoclax, a small-molecule pan-inhibitor of the Bcl2 family. Furthermore, we show that Bcl2 family inhibition synergizes with MEK inhibition as well as with doxorubicin in inducing cell death. Thus, our studies in a novel, relevant mouse model have uncovered a promising druggable feature of aggressive thyroid cancers.
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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.