Thyroid Cancer Molecular Signaling Pathways and Use of Targeted Therapy

Kundra, Priya; Burman, Kenneth D.

doi:10.1016/j.ecl.2007.06.001

Cited by 28 publications

(14 citation statements)

References 41 publications

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“…Several prognostic factors have been suggested as influencing the patient's outcome. Advanced age at diagnosis (greater than 45 years), male gender, large tumour size (C1.5 cm and [4 cm), some histologic subtypes, longer time to therapy, lesser extent of primary surgical treatment, absence of postoperative administration of 131I, greater extrathyroidal extension, lymph node metastases, distant metastases, and some molecular and genetic factors are associated with higher rates of persistence, recurrence and mortality [10][11][12][13][14][15][16][17][18][19][20][21][22]. In contrast, the presence of autoimmune thyroid disease or lymphocytic infiltration may exert a protective effect on the outcome of differentiated thyroid carcinoma patients [15,23,24].…”

Section: Discussionmentioning

confidence: 99%

Prognostic factors and follow-up of patients with differentiated thyroid carcinoma with false negative or nondiagnostic FNAC before surgery. Comparison with a control group

et al. 2011

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Since the clinical implementation of fine needle aspiration cytology (FNAC) to diagnose thyroid carcinoma, few patients remain misdiagnosed and little is known about their clinical outcomes. An observational retrospective study was carried out to analyse prognostic factors and follow-up of patients with differentiated thyroid carcinoma (DTC) not disclosed by FNAC before surgery, compared to a control group. From October 2003 to July 2010, 308 patients underwent surgery as treatment for nodular goitre and 53 had DTC. Cases were 12 subjects with DTC and benign (n = 7) or nondiagnostic (n = 5) FNAC. Controls were 39 subjects with DTC and suspicious (n = 19) or malignant (n = 20) FNAC. Prognostic factors, recurrence and survival rates were compared. Cases had longer time from FNAC to surgery than the control group (86.8 ± 74.1 vs. 16.4 ± 23.8 weeks; P < 0.001), higher prevalence of follicular carcinoma (33.3 vs. 2.6%; P = 0.009), and of two-time total thyroidectomy (75 vs. 30.8%; P = 0.016). Average follow-up was 42.7 ± 25.3 months (2-86 months). There were no deaths. Disease-free survival for cases was 66.9 ± 5.8 months, and for controls 78.7 ± 3.9 months (P: ns). In patients with DTC, the result of the FNAC performed before surgery was not an independent predictor of recurrences or mortality in the first 7 years of follow-up. Thus, false negative or nondiagnostic FNAC in a patient with DTC does not seem to be a primary prognostic factor, but it may reveal other adverse prognostic factors such as longer time to therapy and higher prevalence of follicular carcinoma that may influence long-term outcomes.

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Section: Discussionmentioning

confidence: 99%

Prognostic factors and follow-up of patients with differentiated thyroid carcinoma with false negative or nondiagnostic FNAC before surgery. Comparison with a control group

et al. 2011

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“…These effects are obtained using a concentration of the liposomal drug in a similar range of that described for other agents tested in the same or similar in vitro and in vivo models (Carlomagno et al 2003, Nobuhara et al 2005, Luong et al 2006, Ball et al 2007, targeting the same (ERK-mediated) growthstimulatory pathway, demonstrated to be activated in poorly differentiated and anaplastic thyroid cancer. For some of these novel drugs, clinical trials are currently in progress, alone, or in combination with conventional anticancer drugs (Kundra & Burman 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Most cases are subjected to multimodal treatment regimens based on aggressive surgery, external beam radiation and chemotherapy, but this approach is rarely effective, and the prognosis for these patients is still poor (Ain 1998, Pasieka 2003. However, promising results are being obtained in some patients thanks to combined therapies using novel molecular targeting agents (Kundra & Burman 2007).…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic effects of a novel pyrazolopyrimidine derivative entrapped in liposomes in anaplastic thyroid cancer cells in vitro and in xenograft tumors in vivo

Celano¹,

Schenone²,

Cosco³

et al. 2008

Endocrine Related Cancer

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In this study, we evaluated the activity of two novel pyrazolopyrimidine derivatives (Si 34 and Si 35) against ARO cells, a human anaplastic thyroid cancer cell line. ARO cells exposed to different concentrations of the drugs showed a reduced growth rate and an increase of mortality. After 72 h incubation, doses of 5 and 10 mM Si 34 determined a decrease of cell counts by w25% and w75% compared with those of control cells respectively. Similar findings were observed using Si 35. Treatment with both Si 34 and Si 35 at 10 mM increased cell mortality also (w29% and w18% respectively). At these concentrations, a decrease in cyclin D1 levels was observed. To improve the biopharmaceutical properties, a liposome formulation was prepared. When entrapped in unilamellar liposomes, Si 34 exerted its cytotoxic effects even at lower doses (maximal inhibition at 5 mM) and after shorter incubation time (48 h) either in ARO or other thyroid cancer cell lines. The effects were associated with weak apoptotic death. Inhibition of epidermal growth factorstimulated src and ERK phosphorylation, as well as reduction of migration properties of ARO cells was also observed. Moreover, the growth of tumor xenografts induced in severe combined immunodeficiency (SCID) mice was inhibited by i.v. administration of 25-50 mg/kg of the drug liposomal formulation. In conclusion, the liposomal preparation of this novel pyrazolopyrimidine derivative appears to be a promising tool for the treatment of anaplasic thyroid cancer.

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“…High expression levels of tyrosine kinase receptors for fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor have also been observed in thyroid cancer [23]. Vascular endothelial growth factor, which is known to promote angiogenesis, is thought to play a critical role in tumor growth [24]. Therefore, the inhibition of tyrosine kinase appears a rational target when aiming at stopping the activity of the disease.…”

Section: Discussionmentioning

confidence: 95%

Partial remission of metastatic papillary thyroid carcinoma with sunitinib. Report of a case and review of the literature

Kaldrymides

Kostoglou-Athanassiou

Gkountouvas

et al. 2010

Endocr

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Tyrosine kinase receptors have been implicated in thyroid cancer. Therefore, tyrosine kinase inhibitors may be used for the treatment of advanced metastatic thyroid carcinoma. The aim is to present a case of metastatic papillary thyroid carcinoma responding to the administration of sunitinib, a multi-targeted protein kinase inhibitor. A patient presented with metastatic papillary thyroid carcinoma and hyperthyroidism. After euthyroidism was achieved the patient was treated by the administration of therapeutic radioiodine (131)I, radiotherapy and sunitinib, a multi-targeted tyrosine kinase inhibitor. Thyroglobulin levels decreased from 9,594 to 6,816 ng/ml after 1 month, 6 months later being 2,776 ng/ml. The lesion in the pelvis was 12.5 × 9 cm before treatment decreasing thereafter and the patient improved clinically. The administration of sunitinib resulted in partial disease response in a patient with progressive metastatic papillary thyroid carcinoma. Protein kinase inhibitors may prove useful in the management of advanced metastatic papillary thyroid carcinoma.

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Thyroid Cancer Molecular Signaling Pathways and Use of Targeted Therapy

Cited by 28 publications

References 41 publications

Prognostic factors and follow-up of patients with differentiated thyroid carcinoma with false negative or nondiagnostic FNAC before surgery. Comparison with a control group

Prognostic factors and follow-up of patients with differentiated thyroid carcinoma with false negative or nondiagnostic FNAC before surgery. Comparison with a control group

Cytotoxic effects of a novel pyrazolopyrimidine derivative entrapped in liposomes in anaplastic thyroid cancer cells in vitro and in xenograft tumors in vivo

Partial remission of metastatic papillary thyroid carcinoma with sunitinib. Report of a case and review of the literature

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