Novel treatments for anaplastic thyroid carcinoma

Ferrari, Silvia; Elia, Giusy; Ragusa, Francesca; Ruffilli, Ilaria; Motta, Concettina La; Paparo, Sabrina Rosaria; Patrizio, Armando; Vita, Roberto; Benvenga, Salvatore; Materazzi, Gabriele; Fallahi, Poupak; Antonelli, Alessandro

doi:10.21037/gs.2019.10.18

Cited by 73 publications

(70 citation statements)

References 123 publications

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“…Indeed, with the development of molecular characterization exploring in ATC, researchers have gained better understanding of its molecular pathogenesis in recent years [23]. These drive more novel treatments for anaplastic thyroid carcinoma [12]. Some of the new biological agents have showed potential in the ATC treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Nowadays, small molecule inhibitors targeting multiple tyrosine kinases have attracted great attention because of its clinical bene ts in ATC treatment [12]. Therefore, some of them have been approved by the US FDA for management of different cancers including thyroid cancer such as vandetanib and lenvatinib, and some of them are in the processing of clinical trial [12]. The oral MKI lenvatinib was approved by the FDA in treating radioiodine refractory DTC, and some studies also indicated its modest antitumor effect in ATC patients.…”

Section: Discussionmentioning

confidence: 99%

“…The oral MKI lenvatinib was approved by the FDA in treating radioiodine refractory DTC, and some studies also indicated its modest antitumor effect in ATC patients. However, the using dose should be reduced owing to the grade 3 or higher adverse event [12,14,15]. These results suggested the lenvatinib monotherapy has limited clinical activity in ATC.…”

Section: Discussionmentioning

confidence: 99%

“…Lenvatinib is a multi-target tyrosine kinase inhibitor (MKI) that targets broblast growth factor receptors 1-4 (FGFR1-4), vascular endothelial growth factor receptors 1-3 (VEGFR1-3), c-KIT and RET [10]. It has been approved by FDA and EMA as the second-line treatment for advanced radioiodine-refractory differentiated thyroid carcinoma (DTC) [11,12]. A recent study indicated lenvatinib could signi cantly reduce cell growth and increase apoptosis of ATC cells both in vitro and in vivo [13].…”

Section: Introductionmentioning

confidence: 99%

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Lenvatinib Promotes the Antitumor Effect of Doxorubicin in Anaplastic Thyroid Cancer

Liu

Zhang

et al. 2020

Preprint

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Abstract Background: Anaplastic thyroid cancer (ATC) is a kind of rare thyroid cancer with very poor prognosis. It is one of the deadliest cancers in human due to the aggressive behavior and resistance to treatment. Doxorubicin has been approved in ATC treatment as a single agent, but monotherapy still shows no improvement of the total survival in advanced ATC. Lenvatinib was investigated with encouraging results in treating the patients with radioiodine-refractory differentiated thyroid cancer (DTC). However, antitumor efficacy of combination therapy with lenvatinib and doxorubicin remains largely unclear. Methods: The antitumor efficacy of combination therapy with lenvatinib and doxorubicin on ATC cell proliferation and was assessed by the MTT assay and colony formation. Flow cytometry were employed to assess ATC cells’ apoptosis and cell cycle arrest in response to combination therapy. Xenograft models were used to test its in vivo antitumor activity. Result: Lenvatinib monotherapy was less effective than doxorubicin in treating ATC cell lines and xenografts model. The combination therapy of lenvatinib and doxorubicin significantly inhibited ATC cell proliferation and tumor growth in nude mice, and induced cell apoptosis and cell cycle arrest in compared to lenvatinib or doxorubicin monotherapy. Conclusion: Lenvatinib promotes the antitumor effect of doxorubicin in ATC cell and xenografts model. Lenvatinib/doxorubicin combination may be a potential candidate therapeutic approach for anaplastic thyroid cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lenvatinib Promotes the Antitumor Effect of Doxorubicin in Anaplastic Thyroid Cancer

Liu

Zhang

et al. 2020

Preprint

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“…5 ATC is rare, accounting for only 1% to 2% of all thyroid cancers, but leads to the majority of thyroid cancer-related deaths, making it one of the most aggressive human malignancies. 6,7 Patients diagnosed with ATCs have a median survival of 3-6 months due to its aggressive growth, extrathyroidal invasion, distant metastasis and resistance to conventional treatment. 8,9 To date, there is no standard or effective therapy to prolong the survival of ATC patients.…”

mentioning

confidence: 99%

Melatonin synergizes BRAF‐targeting agent dabrafenib for the treatment of anaplastic thyroid cancer by inhibiting AKT/hTERT signalling

Liao

Gao

Chang³

et al. 2020

J Cellular Molecular Medi

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As a selective inhibitor of BRAF kinase, dabrafenib has shown potent anti‐tumour activities in patients with BRAFV600E mutant anaplastic thyroid cancer. However, the resistance of thyroid cancer cells to dabrafenib limited its therapeutic effect. The effects of melatonin and dabrafenib as monotherapy or in combination on the proliferation, cell cycle arrest, apoptosis, migration and invasion of anaplastic thyroid cancer cells were examined. The molecular mechanism involved in drug combinations was also revealed. Melatonin enhanced dabrafenib‐mediated inhibition of cell proliferation, migration and invasion, and promoted dabrafenib‐induced apoptosis and cell cycle arrest in anaplastic thyroid cancer cells. Molecular mechanistic studies further uncovered that melatonin synergized with dabrafenib to inhibit AKT and EMT signalling pathways. Furthermore, melatonin and dabrafenib synergistically inhibited the expression of hTERT, and the inhibition of cell viability and the induction of cell cycle arrest mediated by the combination of these two drugs were reversed by hTERT overexpression. Taken together, our results demonstrated that melatonin synergized the anti‐tumour effect of dabrafenib in human anaplastic thyroid cancer cells by inhibiting multiple signalling pathways, and provided new insights in exploring the potential therapeutic targets for the treatment of anaplastic thyroid cancer.

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Using NMR Spectroscopy in the Fragment‐Based Drug Discovery of Small‐Molecule Anticancer Targeted Therapies

Diethelm‐Varela

2020

ChemMedChem

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Against the challenge of providing personalized cancer care, the development of targeted therapies stands as a promising approach. The discovery of these agents can benefit from fragment‐based drug discovery (FBDD) methods that help guide ligand design and provide key structural information on the targets of interest. In particular, nuclear magnetic resonance spectroscopy is a promising biophysical tool in fragment discovery due to its detection capabilities and versatility. This review provides an overview of FBDD, describes the basis of NMR‐based fragment screening, summarizes some exciting technical advances reported over the past decades, and closes with a discussion of selected case studies where this technique has been used as part of drug discovery campaigns to produce lead compounds towards the design of anti‐cancer targeted therapies.

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Novel treatments for anaplastic thyroid carcinoma

Cited by 73 publications

References 123 publications

Lenvatinib Promotes the Antitumor Effect of Doxorubicin in Anaplastic Thyroid Cancer

Lenvatinib Promotes the Antitumor Effect of Doxorubicin in Anaplastic Thyroid Cancer

Melatonin synergizes BRAF‐targeting agent dabrafenib for the treatment of anaplastic thyroid cancer by inhibiting AKT/hTERT signalling

Using NMR Spectroscopy in the Fragment‐Based Drug Discovery of Small‐Molecule Anticancer Targeted Therapies

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