Targeted therapy: A new hope for thyroid carcinomas

Perri, Francesco; Pezzullo, Luciano; Chiofalo, Maria Grazia; Lastoria, Secondo; Gennaro, Francesca Di; Scarpati, Giuseppina Della Vittoria; Caponigro, Francesco

doi:10.1016/j.critrevonc.2014.10.012

Cited by 37 publications

(28 citation statements)

References 56 publications

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“…The deregulation of miR-375 was also observed in other malignancies: in medullary thyroid carcinomas (MTC) miR-375 was the strongest up-regulated miRNA (196). Vandetanib is a tyrosine kinase inhibitor for the treatment of patients with recurrent or metastatic MTC that are unresectable, and/or symptomatic (197). Interestingly, miR-375 over-expression associated with SEC23A down-regulation could improve the efficacy of vandetanib (196).…”

Section: A Network Analysis: the Most Central Ncrnas In Chemoresistancementioning

confidence: 99%

The Network of Non-coding RNAs in Cancer Drug Resistance

et al. 2018

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Non-coding RNAs (ncRNAs) have been implicated in most cellular functions. The disruption of their function through somatic mutations, genomic imprinting, transcriptional and post-transcriptional regulation, plays an ever-increasing role in cancer development. ncRNAs, including notorious microRNAs, have been thus proposed to function as tumor suppressors or oncogenes, often in a context-dependent fashion. In parallel, ncRNAs with altered expression in cancer have been reported to exert a key role in determining drug sensitivity or restoring drug responsiveness in resistant cells. Acquisition of resistance to anti-cancer drugs is a major hindrance to effective chemotherapy and is one of the most important causes of relapse and mortality in cancer patients. For these reasons, non-coding RNAs have become recent focuses as prognostic agents and modifiers of chemo-sensitivity. This review starts with a brief outline of the role of most studied non-coding RNAs in cancer and then highlights the modulation of cancer drug resistance via known ncRNAs based mechanisms. We identified from literature 388 ncRNA-drugs interactions and analyzed them using an unsupervised approach. Essentially, we performed a network analysis of the non-coding RNAs with direct relations with cancer drugs. Within such a machine-learning framework we detected the most representative ncRNAs-drug associations and groups. We finally discussed the higher integration of the drug-ncRNA clusters with the goal of disentangling effectors from downstream effects and further clarify the involvement of ncRNAs in the cellular mechanisms underlying resistance to cancer treatments.

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Section: A Network Analysis: the Most Central Ncrnas In Chemoresistancementioning

confidence: 99%

The Network of Non-coding RNAs in Cancer Drug Resistance

et al. 2018

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“…According to histopathological characteristics, thyroid cancer can be classified into differentiated thyroid cancer (DTC) that includes papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC), and anaplastic thyroid cancer (ATC) [2-4]. In general, well-differentiated thyroid cancers have excellent prognosis and 10-year survival rates of 80%-95%, though 2-5% of the patients may develop recurrences and distant metastases with poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Antitumor Effect of BKM120 with Prima-1Met Via Inhibiting PI3K/AKT/mTOR and CPSF4/hTERT Signaling and Reactivating Mutant P53

Xu²,

Li³

et al. 2018

Cell Physiol Biochem

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Background/Aims: PI3KCA and mutant p53 are associated with tumorigenesis and the development of cancers. NVP-BKM120, a selective pan-PI3K inhibitor, exerts the antitumor activity by suppressing the PI3K signaling pathway. Prima-1^Met, a low molecular weight compound, can rescue the gain-of-function of mutant p53 by restoring its transcriptional function. In this study, we investigated whether PI3K inhibition combined with mutant p53 reactivation could enhance the antitumor effect in thyroid cancer cells. Methods: The effects of BKM120 and Prima-1^Met on the proliferation, apoptosis, migration and invasion of thyroid cancer cells were measured by MTT, colony formation, flow cytometry, wound-healing and transwell assays, respectively. Thyroid differentiation was assessed by detecting the expression levels of specific markers using RT-PCR and Western blot. The in vivo antitumor efficacy was analyzed in a mouse xenograft model. Results: The combinational treatment of BKM120 and Prima-1^Met significantly enhanced the inhibitions of cell viability, colony formation, migration and invasion, and the induction of apoptosis in thyroid cell lines, and synergistically suppressed tumor xenograft growth by inhibiting the PI3K/Akt/mTOR and EMT signaling pathways, up-regulating p53 targeted genes, and triggering the release of cytochrome c. Moreover, the combination of BKM120 and Prima-1^Met suppressed the stemlike traits of thyroid cancer cells and promoted their differentiation by upregulating the expression of thyroid-specific differentiation markers and repressing the expression of cancer stem cell markers. Furthermore, the mechanism study demonstrated that the combinational treatment synergistically abrogated the binding of CPSF4 at the promoter of hTERT and thus suppressed hTERT expression. Consistently, overexpression of hTERT rescued the inhibitions of cell viability, invasion and stem-like traits mediated by the combination of BKM120 and Prima-1^Met. Conclusion: Our results showed that the combination of BKM120 with Prima-1^Met synergistically suppressed the growth of thyroid cancer cells and tumor xenografts via inhibiting PI3K/Akt/mTOR and CPSF4/hTERT signaling and reactivating mutant p53.

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“…Perri and coworkers and Manfredi and coworkers described in recent reviews, and Dicitore and coworkers in a recent report, that there are, in fact, several small-molecule inhibitors targeted to thyroid cancer, albeit they have mostly been proven to have small over all effects (Perri et al 2014, Manfredi et al 2015, Dicitore et al 2016. Thus, novel approaches to curtail and stop the progression of aggressive thyroid cancers to a metastatic and terminally fatal disease are urgently warranted.…”

Section: Discussionmentioning

confidence: 99%

“…The available treatments for these forms have shown poor overall effects. Thus, to overcome the difficulties in treating thyroid cancer, new approaches are needed (Haugen & Sherman 2013, Perri et al 2014.…”

Section: Introductionmentioning

confidence: 99%

FTY720 (Fingolimod) attenuates basal and sphingosine-1-phosphate-evoked thyroid cancer cell invasion

Magnusson¹,

Asghar²,

Pulli³

et al. 2016

Endocrine-Related Cancer

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The bioactive lipid sphingosine-1-phosphate (S1P) is a potent inducer of ML-1 thyroid cancer cell migration and invasion. It evokes migration and invasion by activating S1P receptor 1 and 3 (S1P 1,3 ) and downstream signaling intermediates as well as through cross-communication with vascular endothelial growth factor receptor 2 (VEGFR2). However, very little is known about the role of S1P receptors in thyroid cancer. Furthermore, the currently used treatments for thyroid cancer have proven to be rather unsuccessful. Thus, due to the insufficiency of the available treatments for thyroid cancer, novel and targeted therapies are needed. The S1P receptor functional antagonist FTY720, an immunosuppressive drug currently used for treatment of multiple sclerosis, has shown promising effects as an inhibitor of cancer cell proliferation and invasion. In this study, we investigated the effect of FTY720 on invasion and proliferation of several thyroid cancer cell lines. We present evidence that FTY720 attenuated basal as well as S1P-evoked invasion of these cell lines. Furthermore, FTY720 potently downregulated S1P 1 , protein kinase C α (PKCα), PKCβI, and VEGFR2. It also attenuated S1P-evoked phosphorylation of ERK1/2. Our results also showed that FTY720 attenuated S1P-induced MMP2 intracellular expression, S1P-induced secretion of MMP2 and MMP9, and decreased basal MMP2 and MMP9 activity. Moreover, in FTY720-treated cells, proliferation was attenuated, p21 and p27 were upregulated, and the cells were arrested in the G1 phase of the cell cycle. FTY720 attenuated cancer cell proliferation in the chick embryo chorioallantoic membrane assay. Thus, we suggest that FTY720 could be beneficial in the treatment of thyroid cancer.

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Targeted therapy: A new hope for thyroid carcinomas

Cited by 37 publications

References 56 publications

The Network of Non-coding RNAs in Cancer Drug Resistance

The Network of Non-coding RNAs in Cancer Drug Resistance

Synergistic Antitumor Effect of BKM120 with Prima-1Met Via Inhibiting PI3K/AKT/mTOR and CPSF4/hTERT Signaling and Reactivating Mutant P53

FTY720 (Fingolimod) attenuates basal and sphingosine-1-phosphate-evoked thyroid cancer cell invasion

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