Utility of a PI3K/mTOR Inhibitor (NVP-BEZ235) for Thyroid Cancer Therapy

Lin, Shu-Fu; Huang, Yu‐Yao; Lin, Jen‐Der; Chou, Ting‐Chao; Wong, Richard J.

doi:10.1371/journal.pone.0046726

Cited by 38 publications

(34 citation statements)

References 47 publications

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“…All cell lines except KAT4C were authenticated using DNA short tandem repeats profiling and stored in liquid nitrogen until use [33]. BHP7-13, WRO82-1, FRO81-2, KAT18 and KAT4C were maintained in RPMI 1640 with sodium bicarbonate (2.0 g/L).…”

Section: Methodsmentioning

confidence: 99%

Efficacy of an HSP90 inhibitor, ganetespib, in preclinical thyroid cancer models

Lin

Chou

et al. 2017

Oncotarget

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Heat shock protein 90 is a molecular chaperon that maintains the correct folding and function of multiple client proteins. The inhibition of heat shock protein 90, which leads to the simultaneous degradation of multiple proteins involved in oncogenic signaling pathways, has revealed an innovative strategy to treat a variety of cancer types. We evaluated the therapeutic effects of ganetespib, a heat shock protein 90 inhibitor, in treating thyroid cancer. Ganetespib effectively inhibited cell proliferation in a dose-dependent manner in eight cell lines originating from four major histologic types of thyroid cancer (papillary, follicular, anaplastic and medullary). Ganetespib decreased cyclin-dependent kinase 1 and arrested cell cycle progression in G2/M phase. The expression of proteins involved in RAS/RAF/ERK and PI3K/AKT/mTOR signaling pathways was also inhibited. The RET level was decreased in a medullary thyroid cancer cell line. Ganetespib increased Bim expression, activated caspase-3 and induced apoptosis. In vivo, ganetespib retarded the tumor growth of anaplastic and medullary thyroid cancer xenografts with acceptable safety profiles. These findings indicate that ganetespib has potential in the treatment of patients with thyroid cancer.

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Section: Methodsmentioning

confidence: 99%

Efficacy of an HSP90 inhibitor, ganetespib, in preclinical thyroid cancer models

Lin

Chou

et al. 2017

Oncotarget

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“…Several RET/PTC rearrangements (Table 1) have been described, almost exclusively in PTC cells. The exceptions are a few cases of leukemia and lung adenocarcinomas that show peculiar and exclusive RET/ PTC rearrangements that have not yet been reported in PTC (Ballerini et al 2012, Kohno et al 2012, Lira et al 2014, Nakaoku et al 2014. The prevalence of RET/PTCpositive cases is approximately 20%, and it has apparently been decreasing in recent decades (Romei et al 2012).…”

Section: Molecular Alterations In Thyroid Cancer and The Rationale Fomentioning

confidence: 99%

Treatment of advanced thyroid cancer with targeted therapies: ten years of experience

Viola

Valerio

Molinaro

et al. 2016

Endocrine-Related Cancer

167

130

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Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15-20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine. Tyrosine kinase inhibitors (TKIs) represent a new approach to the treatment of advanced cases of RAI-R DTC, MTC, PDTC, and, possibly, ATC. In the past 10 years, several TKIs have been tested for the treatment of advanced, progressive, and RAI-R thyroid tumors, and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC and vandetanib and cabozantinib for MTC. The objective of this review is to present the current status of the treatment of advanced thyroid cancer with the use of innovative targeted therapies by describing both the benefits and the limits of their use based on the experiences reported so far. A comprehensive analysis and description of the molecular basis of these therapies, as well as new therapeutic perspectives, are reported. Some practical suggestions are given for both the choice of patients to be treated and their management, with particular regard to the potential side effects.

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“…Thyroid cancer is also the seventh most common type of cancer in Canadians, and there were ~5,650 cases of thyroid cancer diagnosed in 2012 (1,2). Concurrently, equal trends in the increase in incidence rate have been identified all over the world (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The age-standardized incidence rate of thyroid cancer has increased from 1.1/100,000 to 6.1/100,000 for males, and from 3.3/100,000 to 22.2/100,000 for females, from 1970 to 1972 in the USA (1,15).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effects of adenovirus‑mediated CD and NIS expression combined with Na131I/5‑FC on human thyroid cancer

et al. 2017

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Abstract. Thyroid cancer is the most common type of malignant endocrine tumor diagnosed. Previous studies have indicated that gene therapy is the most promising and effective therapeutic method for thyroid cancer. Therefore, in the present study, Na 131 I/5-fluorocytosine (5-FC) treatment was combined with cytosine deaminase (CD, encoded by the CDA gene) and sodium iodide symporter (NIS, encoded by the SLC5A5 gene) to act together as a therapeutic tool for thyroid cancer. The present study explored the combined cytotoxic effects of adenovirus-mediated CD and NIS under the control of the progression elevated gene-3 (PEG-3) promoter (Ad-PEG-3-CD-NIS) with Na 131 I/5-FC against the human thyroid cancer TT cell line in vitro. The PEG-3 fragment was obtained by polymerase chain reaction (PCR) using rat genomic DNA as the template, and then Ad-PEG-3-CDA-SLC5A5 was constructed using XbaI. TT cells were transfected by recombinant adenovirus. The method of reverse transcription-quantitative PCR was performed to test the expression of CD and NIS at the level of transcription. The morphological change was assessed by fluorescence microscopy and investigated by western blot analysis. An MTT assay was used to determine the number of living cells inhibited by single or combination therapies on TT cells. The results indicated that the PEG-3 was successfully cloned, and was also positively regulated in 293 cells. CDA and SLC5A5 genes were highly expressed in TT cells. Na 131 I combined with 5-FC significantly decreased the human thyroid cancer cells. In conclusion, combination therapy of Ad-PEG3-CDA-SLC5A5 and Na 131 I/5-FC induces significantly more apoptotic characteristics than either single treatment with Ad-PEG-3-CDA-SLC5A5 or Na 131 I/5-FC, and low doses of Ad-PEG-3-CDA-SLC5A5 enhanced the cytotoxic effects.

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Utility of a PI3K/mTOR Inhibitor (NVP-BEZ235) for Thyroid Cancer Therapy

Cited by 38 publications

References 47 publications

Efficacy of an HSP90 inhibitor, ganetespib, in preclinical thyroid cancer models

Efficacy of an HSP90 inhibitor, ganetespib, in preclinical thyroid cancer models

Treatment of advanced thyroid cancer with targeted therapies: ten years of experience

Therapeutic effects of adenovirus‑mediated CD and NIS expression combined with Na131I/5‑FC on human thyroid cancer

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