New therapeutic advances in the management of progressive thyroid cancer

Woyach, Jennifer A.; Shah, Manisha H.

doi:10.1677/erc-08-0335

Cited by 44 publications

(30 citation statements)

References 95 publications

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“…Thus, especially for these latter tumours, efforts to identify molecular markers are extremely important in order to setting up early diagnostic procedures. Moreover, detailed comprehension of molecular mechanisms of thyroid tumorigenesis may be useful to propose novel therapeutic approaches [22,23]. In a previous work, we demonstrated that NPM is overexpressed at an early stage of thyroid tumorigenesis, as a result of a dysregulation occurring at protein levels, thus representing a novel marker of human thyroid tumours [10].…”

Section: Discussionmentioning

confidence: 95%

Nucleophosmin Delocalization in Thyroid Tumour Cells

et al. 2011

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Nucleophosmin (NPM) is a multifunctional nucleolar protein that, depending on the context, can act as oncogene or tumour suppressor. Mutations of the NPM1 gene induce delocalization of NPM in acute myeloid leukaemia. Differently, in solid tumours, only NPM overexpression, but not delocalization, has been so far reported. Here, NPM localization in thyroid tumours was investigated. By using immunohistochemistry, we show increase of NPM cytoplasmic localization in follicular adenomas and papillary carcinomas compared to normal thyroid tissue (p = 0.0125 and <0.0001, respectively). NPM1 mutations commonly found in human leukaemia are not present in thyroid tumours. Immunofluorescence in cultured cell lines was utilized to discriminate between nucleolar and nuclear localization. We show that in thyroid cancer cell lines NPM localizes both in the nucleolus and in nucleus, while in non-tumorigenic thyroid cell lines localizes only in nucleolus. Either presence of the histone deacetylase inhibitor trichostatin A or absence of thyroid-stimulating hormone induces NPM nuclear localization in non-tumorigenic thyroid cell lines.

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Section: Discussionmentioning

confidence: 95%

Nucleophosmin Delocalization in Thyroid Tumour Cells

et al. 2011

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“…ATC has been shown to have multiple pathways overexpressed and actively signaling including: EGFR, phosphorylated Akt (p-Akt), p-ERK and JAK/ STAT pathways (Neff et al, 2008;Sherman, 2006;Smallridge et al, 2009;Woyach and Shah, 2009). Cell cycle progression is coordinated by cyclins and specifically cyclins D1, D3 and E have all been shown to be overexpressed in ATC.…”

Section: Introductionmentioning

confidence: 99%

Foxo3a drives proliferation in anaplastic thyroid carcinoma via transcriptional regulation of cyclin A1: A paradigm shift that impacts current therapeutic strategies

Marlow

Roemeling

Cooper

et al. 2012

Journal of Cell Science

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SummaryThe Forkhead transcription factor, FoxO3a, is a known suppressor of primary tumor growth through transcriptional regulation of key genes regulating cell cycle arrest and apoptosis. In many types of cancer, in response to growth factor signaling, FoxO3a is phosphorylated by Akt, resulting in its exclusion from the nucleus. Here we show that FoxO3a remains nuclear in anaplastic thyroid carcinoma (ATC). This correlates with lack of Akt phosphorylation at serine473 in ATC cell lines and tissues of ATC patients, providing a potential explanation for nuclear FoxO3a. Mechanistically, nuclear FoxO3a promotes cell cycle progression by transcriptional upregulation of cyclin A1, promoting proliferation of human ATC cells. Silencing FoxO3a with a reverse genetics approach leads to downregulation of CCNA1 mRNA and protein. These combined data suggest an entirely novel function for FoxO3a in ATC promotion by enhancing cell cycle progression and tumor growth through transcriptional upregulation of cyclin A1. This is clinically relevant since we detected highly elevated CCNA1 mRNA and protein levels in tumor tissues of ATC patients. Our data indicate therapeutic inactivation of FoxO3a may lead to attenuation of tumor expansion in ATC. This new paradigm also suggests caution in relation to current dogma focused upon reactivation of FoxO3a as a therapeutic strategy against cancers harboring active PI3-K and Akt signaling pathways.

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“…Sunitinib inhibits multiple receptor tyrosine kinases that are implicated in tumor growth, neoangiogenesis, and metastatic progression of cancer. The drug is indicated for unresectable and/or metastatic malignant gastrointestinal stromal tumors after failure of imatinib mesilate treatment due to resistance or intolerance, and the treatment of advanced or metastatic renal cell carcinoma (11)(12)(13).…”

mentioning

confidence: 99%

Hematologic Toxicity in Patients Treated with Sunitinib for Advanced Thyroid Cancer

Gkountouvas

Kostoglou-Athanassiou

Veniou

et al. 2010

Thyroid

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Despite the fact that most patients with DTC had received large doses of radioiodine and some had received external beam radiation therapy, both of which have myelosuppressive potential, treatment with sunitinib was well tolerated in most patients with DTC as well as in the patients with MTC. These results are encouraging, but, as our series was small and did not evaluate efficacy, more extensive studies in DTC and MTC are needed to determine the possible roles of sunitinib in these very different tumors.

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New therapeutic advances in the management of progressive thyroid cancer

Cited by 44 publications

References 95 publications

Nucleophosmin Delocalization in Thyroid Tumour Cells

Nucleophosmin Delocalization in Thyroid Tumour Cells

Foxo3a drives proliferation in anaplastic thyroid carcinoma via transcriptional regulation of cyclin A1: A paradigm shift that impacts current therapeutic strategies

Hematologic Toxicity in Patients Treated with Sunitinib for Advanced Thyroid Cancer

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