Advances in the management of anaplastic thyroid carcinoma: transforming a life-threatening condition into a potentially treatable disease

Califano, Inés; Smulever, Anabella; Jerkovich, Fernando; Pitoia, Fabian

doi:10.1007/s11154-023-09833-1

Cited by 8 publications

(2 citation statements)

References 132 publications

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“…The treatment of advanced thyroid carcinomas as PDTC and ATC with BRAF inhibitor dabrafenib and MEK inhibitor trametinib have shown significant redifferentiation and response rates in BRAF-mutated tumors [70][71][72] . In this study, we examined the effect of isolated dabrafenib and trametinib inhibitors, as well as their combination with PI3K inhibition, on thyroid cancer organoids.…”

Section: Dabrafenib and Trametinib Effect On Redifferentiation Is Pot...mentioning

confidence: 99%

Dual targeting of MAPK and PI3K pathways unlocks redifferentiation ofBraf-mutated thyroid cancer organoids

Lasolle

Schiavo

Tourneur

et al. 2023

Preprint

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Thyroid cancer is the most common endocrine malignancy and several genetic events have been described to promote the development of thyroid carcinogenesis. Besides the effects of specific mutations on thyroid cancer development, the molecular mechanisms controlling tumorigenesis, tumor behavior, and drug resistance are still largely unknown. Cancer organoids have been proposed as a powerful tool to study aspects related to tumor development and progression and appear promising to test individual response to therapies. Here, using mESC-derived thyroid organoids, we developed a BrafV637E-inducible model able of recapitulating the features of papillary thyroid cancer in vitro. Overexpression of BrafV637E rapidly leads to MAPK activation, cell dedifferentiation, and disruption of follicular organization. BrafV637E-expressing organoids show a transcriptomic signature for p53, focal adhesion, ECM-receptor interactions, EMT, and inflammatory signaling pathways. Finally, PTC-like thyroid organoids were used for drug screening assays. The combination of MAPK and PI3K inhibitors reversed Braf oncogene-promoted cell dedifferentiation while restoring thyroid follicle organization and function in vitro. Our results demonstrate that pluripotent stem cells-derived thyroid cancer organoids can mimic tumor development and features while providing an efficient tool for testing novel targeted therapies.

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Section: Dabrafenib and Trametinib Effect On Redifferentiation Is Pot...mentioning

confidence: 99%

Dual targeting of MAPK and PI3K pathways unlocks redifferentiation ofBraf-mutated thyroid cancer organoids

Lasolle

Schiavo

Tourneur

et al. 2023

Preprint

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“…Treatments for ATC, such as radiation therapy, chemotherapy, and radical surgery, have been employed, but their efficacy is limited. Despite recent advances in targeted therapies and immunotherapy and FDA approval of the combination of the BRAF inhibitor dabrafenib and MEK inhibitor trametinib to treat ATC, only limited improvements in survival have been reported . Thus, ATC remains one of the most lethal malignant tumors and no effective treatment is currently available.…”

Section: Introductionmentioning

confidence: 99%

Incorporating Network Pharmacology and Experimental Validation to Identify Bioactive Compounds and Potential Mechanisms of Digitalis in Treating Anaplastic Thyroid Cancer

Zhu,

Liang,

Guo

et al. 2024

ACS Omega

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Anaplastic thyroid cancer (ATC) is one of the most lethal malignant tumors for which there is no effective treatment. There are an increasing number of studies on herbal medicine for treating malignant tumors, and the classic botanical medicine Digitalis and its active ingredients for treating heart failure and arrhythmias have been revealed to have significant antitumor efficacy against a wide range of malignant tumors. However, the main components of Digitalis and the molecular mechanisms of its anti-ATC effects have not been extensively studied. Here, we screened the main components and core targets of Digitalis and verified the relationship between the active components and targets through network pharmacology, molecular docking, and experimental validation. These experiments showed that the active ingredients of Digitalis inhibit ATC cell activity and lead to ATC cell death through the apoptotic pathway.

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Efficacy and safety of BRAF/MEK inhibitors in BRAFV600E-mutated anaplastic thyroid cancer: a systematic review and meta-analysis

Priantti,

Rodrigues,

de Moraes

et al. 2024

Endocrine

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Advances in the management of anaplastic thyroid carcinoma: transforming a life-threatening condition into a potentially treatable disease

Cited by 8 publications

References 132 publications

Dual targeting of MAPK and PI3K pathways unlocks redifferentiation ofBraf-mutated thyroid cancer organoids

Dual targeting of MAPK and PI3K pathways unlocks redifferentiation ofBraf-mutated thyroid cancer organoids

Incorporating Network Pharmacology and Experimental Validation to Identify Bioactive Compounds and Potential Mechanisms of Digitalis in Treating Anaplastic Thyroid Cancer

Efficacy and safety of BRAF/MEK inhibitors in BRAFV600E-mutated anaplastic thyroid cancer: a systematic review and meta-analysis

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