FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2068695977> ?p ?o ?g. }

• W2068695977 endingPage "x333" @default.
• W2068695977 startingPage "x328" @default.
• W2068695977 abstract "Thyroid cancer (TC) is uncommon, although it represents the most frequently occurring malignancy of the endocrine system. Over the last few years, the incidence of TC has been increasing in some European countries [1.Reynolds R.M. Weir J. Stockton D.L. Changing trends in incidence and mortality of thyroid cancer in Scotland.Clin Endocrinol (Oxf). 2005; 62: 156-162Crossref PubMed Scopus (169) Google Scholar, 2.Leenhardt L. Grosclaude P. Cherie-Challine L. Increased incidence of thyroid carcinoma in France: a true epidemic or thyroid nodule management effects? Report from the french thyroid cancer committee.Thyroid. 2004; 14: 1056-1060Crossref PubMed Scopus (322) Google Scholar, 3.Smailyte G. Miseikyte-Kaubriene E. Kurtinaitis J. Increasing thyroid cancer incidence in Lithuania in 1978–2003.BMC Cancer. 2006; 6: 284Crossref PubMed Scopus (58) Google Scholar], in United States [4.Davies L. Welch H.G. Increasing incidence of thyroid cancer in the United States, 1973–2002.JaMa. 2006; 295: 2164-2167Crossref PubMed Scopus (2598) Google Scholar] and Canada. Most of the TCs are differentiated carcinomas (DTCs) (95%) that derive from the follicular epithelial cells and they are either papillary (PTC) (80%), follicular (FTC) (10%) and Hurthle cell (5%) thyroid carcinomas. Survival rates can be very different, accounting for their different phenotypes and radioiodine sensitivity. another 5% are the neuroendocrine-derived medullary carcinomas (MTCs) and 1% are anaplastic carcinomas. Standard therapies for patients with advanced DTC include surgery, radioactive iodine 131 (RaI) and thyroid-stimulating hormone (TSH) suppression. For MTC, surgery represents the only recognised form of curative approach. RaI and TSH suppression play no role in MTCs. anaplastic carcinoma is primarily treated with surgery, when feasible, and radiotherapy or chemoradiation. In TC, the probability of cure depends on the histotype, the tumour stage and the RaI sensitivity. Even within the same histotype, mainly DTC and MTC, there are marked differences in relation to survival, which are explained by the biological heterogeneity. Once MTCs develop distant metastases and DTCs lose their ability to uptake iodine (25%–50%) or in case they are intrinsically RaI refractory, treatment opportunities are very few, since active chemotherapy agents are lacking. Doxorubicin (adriamycin), cisplatin and dacarbazine (DTIC-Dome) based chemotherapy obtained a low response rate [5.Shimaoka K. Schoenfeld Da DeWys W.D. a randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma.Cancer. 1985; 56: 2155-2160Crossref PubMed Scopus (360) Google Scholar, 6.Sherman S.I. Thyroid carcinoma.Lancet. 2003; 361 (10): 501-511Abstract Full Text Full Text PDF PubMed Scopus (873) Google Scholar, 7.Cooper S.D. Doherty M.G. Bryan R. et al.Revised american thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.Thyroid. 2009; 19: 1167-1214doi:10.1089/thy.2009.0110Crossref PubMed Scopus (5281) Google Scholar]. RaI-resistant thyroid carcinomas, metastatic medullary and anaplastic thyroid carcinomas (aTCs) represent one of the most appealing models for biological therapies. Recent years have been characterised by significant advances in the understanding of the molecular basis of thyroid carcinogenesis. Many tumour-initiating genetic events have been already identified in TC. Interestingly, there is a typical morphological and histopathological disease presentation that consistently correlates with specific molecular pathway deregulation and some of its features are associated with more aggressive tumour behaviour. Gene deregulation is responsible for unique PTC, FTC and MTC gene expression signatures (see below) that confer a distinct phenotype and biological properties. On the other hand, the activation of ubiquitous intracellular tumour growth pathways, such as mitogen-activated protein kinase (MaPK) signalling and phosphatidylinositol-3-kinase (PI3K)/akt, is also involved. Other “not specific” alterations, such as loss of heterozygosity, PI3K/akt signalling pathway mutations and those involving catenin (cadherin-associated protein), beta 1, 88kDa (CTNNB1), RaS and phosphatase and tensin homolog (PTEN), are more frequently associated with poorly DTCs or aTC. This latter can arise de novo or from a pre-existing PTC or FTC, although these alterations can be considered as a marker of tumour progression within a stepwise process rather than an initiating one. Supporting evidence to this is based on microarray studies that have identified genes and pathways preferentially deregulated in aTC, when compared with differentiated tumours. Rearranged during transfection (RET) PTC oncogenes play a causative role in the pathogenesis of 5%–30% of sporadic adult PTCs [8.Bongarzone I. Vigneri P. Mariani L. RET/NTRK1 rearrangements in thyroid gland tumors of the papillary carcinoma family: correlation with clinicopathological features.Clin Cancer Res. 1998; 4: 223-228PubMed Google Scholar, 9.Santoro M. Carlomagno F. Hay I.D. et al.Ret oncogene activation in human thyroid neoplasms is restricted to the papillary cancer subtype.J Clin Invest. 1992; 89: 1517-1522Crossref PubMed Scopus (335) Google Scholar], while a higher percentage is recorded in tumours in children and young adults [10.Fenton C.L. Lukes Y. Nicholson D. The ret/PTC mutations are common in sporadic papillary thyroid carcinoma of children and young adults.J Clin Endocrinol Metab. 2000; 85: 1170-1175Crossref PubMed Scopus (209) Google Scholar] and in individuals exposed to either accidental or therapeutic irradiation (50%–80%) [11.Bounacer A. Wicker R. Caillou B. et al.High prevalence of activating ret proto-oncogene rearrangements, in thyroid tumors from patients who had received external radiation.Oncogene. 1997; 15: 1263-1273Crossref PubMed Scopus (268) Google Scholar, 12.Rabes H.M. Demidchik E.P. Sidorow J.D. et al.Pattern of radiation-induced RET and NTRK1 rearrangements in 191 post-chernobyl papillary thyroid carcinomas: biological, phenotypic, and clinical implications.Clin Cancer Res. 2000; 6: 1093-1103PubMed Google Scholar]. RET/PTC oncogenes are produced by chromosomal rearrangements involving the RET proto-oncogene, encoding a kinase receptor binding the glial cell line-derived neurotrophic factor family of peptides. all types of RET/PTC oncogenes have in common the replacement of the extracellular ligand-binding domain of RET by RET-fused genes, which are expressed in the thyrocytes and encode proteins containing dimerisation domains; this property allows constitutive, ligand-independent activation of RET kinase leading to clonal expansion and neoplastic transformation of the thyroid follicular cells. Thirteen different RET/PTC oncogenes have been so far described both in sporadic and in radiation-derived PTCs, RET/PTC1 is the most frequent rearrangement in general TC population, while RET/PTC3 is most involved in case of radiation-derived PTCs and in tall-cell variant carcinomas [13.Nikiforova M.N. Nikiforov Y.E. Molecular genetics of thyroid cancer: implications for diagnosis, treatment and prognosis.Expert Rev Mol Diagn. 2008; 8: 83-95Crossref PubMed Scopus (227) Google Scholar]. RET/PTC oncogenes trigger the activation of multiple intracellular signal transduction pathways, including the MaPK pathway. It is still not clarified how the different types of RET rearrangements can affect the clinical behaviour of PTC. The distribution of the RET/PTC gene can be heterogenous among the tumour cells (clonal versus non-clonal). In this context, tumour heterogeneity characterised by non-clonal RET distribution can lead to treatment resistance by employing drugs that specifically inhibit RET. activating point mutations of the RET proto-oncogene are observed in both the hereditary (95% of multiple endocrine neoplasia (MEN) 2 families) and sporadic forms (30%–50%) of MTC. These mutations cause constitutive, ligand-independent activation of RET tyrosine kinase (TK) activity and, in some case, they alter the RET substrate specificity. Mutations at different codons of RET are associated with the biological aggressiveness of the tumour [14.Hubner Ra Houlston R.S. Molecular advances in medullary thyroid cancer diagnostics.Clin Chim acta. 2006; 370: 2-8Crossref PubMed Scopus (28) Google Scholar] and they may display a different affinity for the TK inhibitors (TKIs). another genetic alterations involved in the early pathogenesis of TC is the activation of BRaF. BRaF is one of three mammalian isoforms of the serine-threonine Raf kinase family, which are intracellular effectors of the MaPK signal cascade. The BRaF gene is frequently mutated in a wide range of human cancers. The prevalent mutation is the V600E, which increases the BRaF basal kinase activity, resulting in constitutive activation and continuous phosphorylation of downstream effectors of the MaPK pathway [15.Xing M. BRaF mutation in thyroid cancer.Endocr Relat Cancer. 2005; 12: 245-262Crossref PubMed Scopus (1030) Google Scholar]. The BRaFV600E mutation represents the most common genetic change in PTC, reported in up to 70% of cases [16.Kloos R.T. Ringel M.D. Knopp M.V. et al.Phase II trial of sorafenib in metastatic thyroid cancer.J Clin Oncol. 2009; 10: 1675-1684Crossref Google Scholar, 17.Wan P.T. Garnett M.J. Roe S.M. et al.Mechanism of activation of the RaF-ERK signaling pathway by oncogenic mutations of BRaF.Cell. 2004; 116: 855-867Abstract Full Text Full Text PDF PubMed Scopus (2185) Google Scholar]. Other and rare mechanisms, such as different point mutations, small insertions and deletions and gene rearrangements, contribute to BRaF oncogenic activation in PTCs. Some of these alterations have been associated with radiation-induced tumours. BRaF V600E has a recognised prognostic role and it could represent also a key factor for PTC management. BRaF V600E mutation is also present in up to 24% of aTCs arising in association with PTCs [18.Nikiforova M.N. Kimura E.T. Gandhi M. et al.BRaF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas.J Clin Endocrinol Metab. 2003; 88: 5399-5404Crossref PubMed Scopus (837) Google Scholar, 19.Xing M. Westra W.H. Tufano R.P. et al.BRaF mutation predicts a poorer clinical prognosis for papillary thyroid cancer.J Clin Endocrinol Metab. 2005; 90: 6373-6379Crossref PubMed Scopus (782) Google Scholar]. BRaF mutation in fine-needle aspiration diagnostic biopsies could be useful to drive decisions on surgical extension [20.Xing M. Clark D. Guan H. et al.BRaF mutation testing of thyroid fine-needle aspiration biopsy specimens for preoperative risk stratification in papillary thyroid cancer.J Clin Oncol. 2009; 27: 2977-2982Crossref PubMed Scopus (221) Google Scholar]. Moreover, the detection of free circulating mutant BRaF in serum [21.Chuang T.C. Chuang Ay Poeta L. Detectable BRaF mutation in serum DNa samples from patients with papillary thyroid carcinomas.Head Neck. 2010; 32: 229-234PubMed Google Scholar] could be employed as a non-invasive diagnostic tool. RaI resistance in BRaF-mutated tumours has been associated with deregulation of genes involved in the movement and metabolisation of iodine in follicular cells. Moreover, since BRaF is downstream of RET and Ras pathway, its inhibition can be effective in tumours with upstream RET and Ras mutations. RaS point mutations occur rarely in PTC (10%) [22.Melillo R.M. Castellone M.D. Guarino V. et al.The RET/PTCRaS-BRaF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells.J Clin Invest. 2005; 115: 1068-1081Crossref PubMed Scopus (294) Google Scholar], most frequently in FTC (up to 50%) and in poorly undifferentiated carcinomas [23.Garcia-Rostan G. Zhao H. Camp R.L. et al.Ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer.J Clin Oncol. 2003; 21: 3226-3235Crossref PubMed Scopus (305) Google Scholar]. Some studies have reported a correlation between RaS mutations and dedifferentiation, probably due to chromosomal instability as well as less favourable prognosis in DTC. RaS genes (HRaS, KRaS and NRaS) encode highly related small G proteins playing a central role in intracellular signalling. The mutant Ras becomes permanently switched in the active status, thus constitutively activating their downstream targets, leading to the activation of MaPK and PI3K/akt pathways. Mutations on BRaF and RaS, and RET-rearrangements, which involve about 70% of PTCs, trigger MaPK signalling. Interestingly, they are mutually exclusive and rarely expressed simultaneously within the same tumour [22.Melillo R.M. Castellone M.D. Guarino V. et al.The RET/PTCRaS-BRaF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells.J Clin Invest. 2005; 115: 1068-1081Crossref PubMed Scopus (294) Google Scholar], indicating that a single oncogenic hit in this kinase cascade is enough for PTC development [24.Kimura E.T. Nikiforova M.N. Zhu Z. High prevalence of BRaF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RaS-BRaF signaling pathway in papillary thyroid carcinoma.Cancer Res. 2003; 63: 1454-1457PubMed Google Scholar]. another chromosomal aberration that can result in TC tumourigenesis is the PaX8-PPaR (peroxisome proliferator-activated receptor) gamma gene rearrangement. This alteration is frequently seen in FTCs up to 60% of the cases and tends to be present in tumours with a vascular invasion. an inappropriate activation of MET has been described in many malignant tumours, including medullary TC. MET gene amplification enhances the survival and the invasive advantage of neoplastic cells, and its activation is generally the consequence rather than the cause of cancer features: e.g. in MTC, RET can induce a transcriptional up-regulation and activation of MET. a close cooperation between MET and vascular endothelial growth factor (VEGF) to promote neo-angiogenesis, cell motility and survival has been demonstrated [24.Kimura E.T. Nikiforova M.N. Zhu Z. High prevalence of BRaF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RaS-BRaF signaling pathway in papillary thyroid carcinoma.Cancer Res. 2003; 63: 1454-1457PubMed Google Scholar]. Moreover, the inhibition of MET seems to selectively modulate the activity of RaS dependent signals, leaving the other pathways unaltered. Recent evidence on cell lines have demonstrated that silencing of MET results in the arrest of tumour growth, regression of metastases and decreased generation of new metastases, suggesting the importance of MET expression [25.Boccaccio C. Comoglio PM Invasive growth: a MET-driven genetic programme for cancer and stem cells.Nat Rev Cancer. 2006; 6: 637-645Crossref PubMed Scopus (454) Google Scholar] in cancer development and therefore as a target for tailored drugs. The VEGF is the main stimulator of angiogenesis in the thyroid gland and elevated levels of VEGF have been found in thyroid tumour tissue than in normal thyroid [26.Soh E.Y. Duh Q.Y. Sobhi Sa et al.Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid.J Clin Endocrinol Metab. 1997; 82: 3741-3747Crossref PubMed Scopus (147) Google Scholar]. The VEGF binds VEGF receptor-1 (VEGFR-1, fms-like TK-1) and VEGFR-2 (fetal liver kinase-1/kinase insert domain-containing receptor), which in turn activate MaPK signalling [27.Ferrara N. VEGF as a therapeutic target in cancer.Oncology. 2005; 69: 11-16Crossref PubMed Scopus (478) Google Scholar]. The intensity of VEGF expression is related to PTC with a higher risk of metastasis and recurrence, and a shorter disease-free survival [28.Klein M. Vignaud J.M. Hennequin V. et al.Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma.J Clin Endocrinol Metab. 2001; 86: 656-658Crossref PubMed Scopus (0) Google Scholar, 29.Lennard C.M. Patel A. Wilson J. et al.Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer.Surgery. 2001; 129: 552-558Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar]. It seems that other pathways, such as VEGFR- and epidermal growth factor receptor (EGFR)-dependent signalling, also participate in tumour growth and development [30.Croyle M. akeno N. Knauf Ja et al.RET/PTCinduced cell growth is mediated in part by epidermal growth factor receptor (EGFR) activation: evidence for molecular and functional interactions between RET and EGFR.Cancer Res. 2008; 68: 4183-4191Crossref PubMed Scopus (84) Google Scholar]. It has been shown that overexpression and activation of EGFR and VEGFR-2 were more pronounced in metastatic tissue from MTCs rather than the primary tumour with a tendency towards a differential EGFR expression in relation to more aggressive RET mutations [31.Rodriguez-antona C. Pallares J. Montero-Conde C. et al.Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis.Endocr Relat Cancer. 2010; 17: 7-16Crossref PubMed Scopus (92) Google Scholar]. Moreover, a dual inhibition of the EGFR and VEGFR is required to induce apoptosis and inhibit proliferation, independent of the activating mutation present, in thyroid cell lines [32.Hoffmann S. Glaser S. Wunderlich A. et al.Targeting the EGF/VEGF-R system by tyrosine-kinase inhibitors––a novel antiproliferative/antiangiogenic strategy in thyroid cancer.Langenbecks arch Surg. 2006; 391: 589-596Crossref PubMed Scopus (32) Google Scholar]. The concept of ‘oncogene addiction’ describes the phenomenon by which some cancers, containing multiple genetic abnormalities, appear to be dependent on a single over-active oncogene for their proliferation and survival. at present, this is the keystone for effective target therapy and in TC the concept holds on. Multiple oncogenes have been identified and many targeted agents are currently available and many others are under investigation. MTC cells are, for example, addicted to oncogenic RET signalling but the RET-TKIs used in clinical trials, which showed promising activity, are not exclusively targeted at RET. This raises two questions: first, what are the real targets? and second, what is the best possible combination of drugs to improve efficacy, tackle primary and reduce acquired resistance? Clinical trials are often requiring a confirmed progressive disease according to RECIST [33.Therasse P. arbuck S.G. Eisenhauer Ea et al.New guidelines to evaluate the response to treatment in solid tumors. European Organization for research and treatment of cancer.J Natl Cancer Inst. 2000; 92: 205-216Crossref PubMed Scopus (14316) Google Scholar, 34.Eisenhauer Ea Therasseb P. Bogaertsc J. et al.New response evaluation criteria in solid tumours: revised RECIST guideline.Eur J Cancer. 2009; 45: 228-247Abstract Full Text Full Text PDF PubMed Scopus (16973) Google Scholar] as inclusion clinical criteria. Interestingly, there is no univocal definition of how many months are required to define a progressive disease to enter a clinical trial for both DTC and MTC. although, the criteria are clearly adopted because of the TC's natural history and the primary end-point of the trials (which is often progression-free survival, PFS), a correlation between the time frame of progression before entering the study and the outcome has never been attempted which would, at least, validate its relevance. For future trials, this will have to be standardised. In DTC studies, among the inclusion criteria, a RaI-resistant/refractory disease defined as the absence of 131I uptake on any radioiodine scan; one or more lesions with progressive disease despite 131I uptake or a cumulative activity delivered of 131I >600 mCi are required. Correctly, biochemical progression is not considered within the inclusion criteria. In our opinion, RaI-resistant/refractory tumours need to be better defined since this has been clearly associated with a specific tumour biological profile that could correlate with target drug's activity. Table 1 reports the molecules inhibiting thyroid-specific oncogenic kinases with promising results seen mainly within phase I studies. BRaF inhibitors are the only specific target agents that have been clinically tested. Prospective phase II studies are ongoing. The other studied agents have no specific target since they inhibit VEGFR and other kinases.Table 1Studies with molecules inhibiting thyroid-specific oncogenic kinasesagentSite of activityNo. of patientsOutcomevemurafenib [50.Flaherty K. Puzanov I. Sosman J. et al.Phase I study of PLX4032: proof of concept for V600E BRaF mutation as a therapeutic target in human cancer.J Clin Oncol. 2009; 27: 461sGoogle Scholar]BRaF mutant V600E3 with PTC with mut BRaF1 PR, 2 prolonged SDXL281 [51.Schwartz G. Yazji S. Menedelson D.S. et al.a phase 1 study of XL281, a potent and selective inhibitor of RaF kinases, administered orally to patients with advanced solid tumors.2008Crossref Google Scholar]BRaF mutant + wild type54 prolonged SDPR, partial response; SD, stable disease. Open table in a new tab PR, partial response; SD, stable disease. a list of the important study features along with the results according to the histological type are reported in Table 2. In general, not only activity but also toxicity profiles are common among all these agents, including fatigue, cardiovascular (hypertension, asymptomatic QT interval prolongation and thromboembolism), gastrointestinal (diarrhoea, nausea and very rare cases of perforation) and muco-cutaneous (hand foot syndrome, skin rash, stomatitis, dysphonia, photosensitivity, keratoacanthomas and malignant squamous cell lesion) [35.Hong D.S. Reddy S.B. Prieto V.G. et al.Multiple squamous cell carcinomas of the skin after therapy with sorafenib combined with tipifarnib.arch Dermatol. 2008; 144: 779-782Crossref PubMed Scopus (45) Google Scholar]. Hypothyroidism is a remarkable side-effect, experienced with motesanib [36.Sherman S.I. Wirth L.J. Droz J.P. et al.Motesanib diphosphate in progressive differentiated thyroid cancer.N Engl J Med. 2008; 359: 31-42Crossref PubMed Scopus (409) Google Scholar, 37.Kloos R.T. Ringel M.D. Knopp M.V. et al.Phase II trial of sorafenib in metastatic thyroid cancer.J Clin Oncol. 2009; 27: 1675-1684Crossref PubMed Scopus (461) Google Scholar], sorafenib [38.Gupta-abramson V. Troxel Ab Nellore A. et al.Phase II trial of sorafenib in advanced thyroid cancer.J Clin Oncol. 2008; 26: 4714-4719Crossref PubMed Scopus (560) Google Scholar], imatinib [39.de Groot J.W. Zonnenberg Ba van Ufford-Mannesse P.Q. et al.a phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma.J Clin Endocrinol Metab. 2007; 92: 3466-3469Crossref PubMed Scopus (146) Google Scholar] and sunitinib [40.Wong E. Rosen L.S. Mulay M. et al.Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity.Thyroid. 2007; 17: 351-355Crossref PubMed Scopus (163) Google Scholar], vandetanib requiring adjustments in the dosage of thyroid hormone replacement therapy. acute cholecystitis is a very rare (5%) adverse event occurring during motesanib administration, for which the correlation with the drug assumption is still unknown [36.Sherman S.I. Wirth L.J. Droz J.P. et al.Motesanib diphosphate in progressive differentiated thyroid cancer.N Engl J Med. 2008; 359: 31-42Crossref PubMed Scopus (409) Google Scholar, 41.Leboulleux S. Bastholt L. Krause T.M. et al.Vandetanib in locally advanced or metastatic differentiated thyroid cancer (papillary; follicular; DTC): a randomized, double-blind phase II trial.2010Google Scholar]. Similar to other target therapies, toxic effects commonly recover by the drug withheld. None of these toxic effects can be considered as a surrogate marker of efficacy while, on the other hand, toxicity intensity often correlates with treatment interruptions, raising the question on the optimal long-term tumour exposure in order to maximise therapeutic effects. Interestingly, mostly in MTC patients, the assumption of TKI causes an immediate relief of disease-related symptoms such as diarrhoea, regardless of the response.Table 2Phase II clinical trials with multitarget agents in radioactive iodine 131(RaI)-resistant DTC, metastatic MTC and aTCauthorHistotypeDrugNo. of patients assessable for responseResponse rate (RR)Frank-Raue et al. [52.Frank-Raue K. Fabel M. Delorme S. Efficacy of imatinib mesylate in advanced medullary thyroid carcinoma.Eur J Endocrinol. 2007; 157: 215-220Crossref PubMed Scopus (84) Google Scholar]MTC = 8Imatinib90%hMTC = 1de Groot et al. [39.de Groot J.W. Zonnenberg Ba van Ufford-Mannesse P.Q. et al.a phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma.J Clin Endocrinol Metab. 2007; 92: 3466-3469Crossref PubMed Scopus (146) Google Scholar]MTC = 15150%Ha [53.Ha H.T. Lee J.S. Urba S. et al.Phase II trial evaluating imatinib (I) in patients (pts) with anaplastic thyroid carcinoma (aTC).J Clin Oncol. 2009; 27: 315sGoogle Scholar]aTC = 111125%Cohen et al. [54.Cohen E.E. Needles B.M. Cullen K.J. et al.Phase 2 study of sunitinib in refractory thyroid cancer.J Clin Oncol. 2008; 26 (abstr 6025)Crossref Google Scholar]PTC = 37Sunitinib43 (38)a13% (18%)aCohen et al. [55.Cohen EE, Kanagarajan J, Tinich C et al. Sunitinib in patients with radioactive iodine refractory and progressive differentiated thyroid cancer: a phase 2 study. Presented at the World Congress on Thyroid Cancer, vol. 60. Abstract 051, August 6–10; 2009.Google Scholar]MTC = 6Ravaud et al. [56.Ravaud A. de la Fouchardiere C. Courbon F. et al.Sunitinib in patients with refractory advanced thyroid cancer: the THYSU phase II trial.J Clin Oncol. 2008; 26: 330sPubMed Google Scholar]PTC = 8175%MTC = 4aTC = 1Other = 4Goulart et al. [57.Goulart B. Carr L. Martins R.G. et al.Phase II study of sunitinib in iodine refractory, well differentiated thyroid cancer (WDTC) and metastatic medullary thyroid carcinoma (MTC).J Clin Oncol. 2008; 26: 331sGoogle Scholar]DTC = 151844% (FDG response)MTC = 3Carr et al. [58.Carr L. Goulart B. Martins R.G. et al.Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation.Clin Cancer Res. 2010; 16: 5260-5268Crossref PubMed Scopus (325) Google Scholar]DTC = 262938%MTC = 7Sherman et al. [36.Sherman S.I. Wirth L.J. Droz J.P. et al.Motesanib diphosphate in progressive differentiated thyroid cancer.N Engl J Med. 2008; 359: 31-42Crossref PubMed Scopus (409) Google Scholar]PTC = 54Motesanib9314%FTC = 15HCT = 17Other = 7Schlumberger [42.Schlumberger M.J. Elisei R. Bastholt L. et al.Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer.J Clin Oncol. 2009; 27(23): 3794-3801Crossref Scopus (299) Google Scholar]MTC = 91912%Kloos et al. [37.Kloos R.T. Ringel M.D. Knopp M.V. et al.Phase II trial of sorafenib in metastatic thyroid cancer.J Clin Oncol. 2009; 27: 1675-1684Crossref PubMed Scopus (461) Google Scholar]arm a PTC = 41Sorafenib41arm a = 15%arm B non-PTC = 1111arm B = 0%Gupta-abramson et al. [38.Gupta-abramson V. Troxel Ab Nellore A. et al.Phase II trial of sorafenib in advanced thyroid cancer.J Clin Oncol. 2008; 26: 4714-4719Crossref PubMed Scopus (560) Google Scholar]PTC = 183023% RPFTC = 9MTC = 1aTC = 1Brose et al. [48.Brose M.S. Troxel Ab Redlinger M. et al.Effect of BRaFV600E on response to sorafenib in advanced thyroid cancer patients.J Clin Oncol. 2009; 27Google Scholar]PTC = 2552 (55)aProgression-free survival (PFS) 84 weeksFTC = 19MTC = 4aTC = 5Nagaiah et al. [60.Nagaiah G. Fu P. Wasman J.K. et al.Phase II trial of sorafenib (bay 43-9006) in patients with advanced anaplastic carcinoma of the thyroid (aTC).J Clin Oncol. 2009; 27: 315sGoogle Scholar]aTC = 151513%Lam et al. [61.Lam E.T. Ringel M.D. Kloos R.T. et al.Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer.J Clin Oncol. 2010; 28: 2323-2330Crossref PubMed Scopus (313) Google Scholar]MTC = 161911%hMTV = 3Kober et al. [62.Kober F. Hermann M. Handler A. et al.Effect of sorafenib in symptomatic metastatic medullary thyroid cancer.J Clin Oncol. 2007; 25: 14065Crossref Google Scholar]MTC = 5540%Wells et al. [63.Wells Sa Gosnell J.E. Gagel R.F. et al.Vandetanib in metastatic hereditary medullary thyroid cancer: follow-up results of an open-label phase II trial.am Soc Clin Oncol. 2007; 25: 303sGoogle Scholar]hMTCVandetanib3020%Haddad et al. [64.Haddad R.I. Krebs Ad Vasselli J. a phase II open-label study of vandetanib in patients with locally advanced or metastatic hereditary medullary thyroid cancer.J Clin Oncol. 2008; 26: 322sGoogle Scholar]hMTC1916%Fox et al. [65.Fox E. Widemann B.C. Whitcomb P.O. et al.Phase I/II trial of vandetanib in children and adolescents with hereditary medullary thyroid carcinoma.Curr Opin Oncol. 2009; 27: 522SGoogle Scholar]hMTC (children, young adults)728%Cohen et al. [66.Cohen E.E. Rosen L.S. Vokes E.E. et al.axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study.J Clin Oncol. 2008; 26: 4708-4713Crossref PubMed Scopus (533) Google Scholar]PTC = 29axitinib6030%FTC = 15PFS 18.1 monthsMTC = 12aTC = 2unk = 2Locati et al. [67.Locati L, Licitra L, Agate L et al. Phase 2 trial of axitinib for advanced thyroid cancer: preliminary activity results. 5th European Conference on Head & Neck Oncology 2012; Abstr" @default.
• W2068695977 created "2016-06-24" @default.
• W2068695977 creator A5005945571 @default.
• W2068695977 creator A5014239599 @default.
• W2068695977 creator A5018624121 @default.
• W2068695977 creator A5041423129 @default.
• W2068695977 creator A5047193688 @default.
• W2068695977 date "2012-09-01" @default.
• W2068695977 modified "2023-09-26" @default.
• W2068695977 title "Multikinase inhibitors in thyroid cancer" @default.
• W2068695977 cites W1847774702 @default.
• W2068695977 cites W1933537883 @default.
• W2068695977 cites W1940998999 @default.
• W2068695977 cites W1978311359 @default.
• W2068695977 cites W1982618742 @default.
• W2068695977 cites W1985147573 @default.
• W2068695977 cites W1985995844 @default.
• W2068695977 cites W1986163748 @default.
• W2068695977 cites W1999966784 @default.
• W2068695977 cites W2007193634 @default.
• W2068695977 cites W2011326694 @default.
• W2068695977 cites W2016417793 @default.
• W2068695977 cites W2019607817 @default.
• W2068695977 cites W2024570610 @default.
• W2068695977 cites W2033043245 @default.
• W2068695977 cites W2033882181 @default.
• W2068695977 cites W2035750944 @default.
• W2068695977 cites W2036011846 @default.
• W2068695977 cites W2051963942 @default.
• W2068695977 cites W2052688111 @default.
• W2068695977 cites W2068453322 @default.
• W2068695977 cites W2070563197 @default.
• W2068695977 cites W2089327677 @default.
• W2068695977 cites W2092846304 @default.
• W2068695977 cites W2099814925 @default.
• W2068695977 cites W2100542906 @default.
• W2068695977 cites W2101642991 @default.
• W2068695977 cites W2104875539 @default.
• W2068695977 cites W2106695112 @default.
• W2068695977 cites W2108668400 @default.
• W2068695977 cites W2109544257 @default.
• W2068695977 cites W2112129582 @default.
• W2068695977 cites W2112475888 @default.
• W2068695977 cites W2114293271 @default.
• W2068695977 cites W2115068822 @default.
• W2068695977 cites W2116542352 @default.
• W2068695977 cites W2118986295 @default.
• W2068695977 cites W2119501407 @default.
• W2068695977 cites W2123534406 @default.
• W2068695977 cites W2124662474 @default.
• W2068695977 cites W2126932086 @default.
• W2068695977 cites W2133354058 @default.
• W2068695977 cites W2134638316 @default.
• W2068695977 cites W2135738209 @default.
• W2068695977 cites W2137488285 @default.
• W2068695977 cites W2139248078 @default.
• W2068695977 cites W2142173193 @default.
• W2068695977 cites W2143053648 @default.
• W2068695977 cites W2145150141 @default.
• W2068695977 cites W2145455579 @default.
• W2068695977 cites W2148097572 @default.
• W2068695977 cites W2148154962 @default.
• W2068695977 cites W2149935230 @default.
• W2068695977 cites W2155008672 @default.
• W2068695977 cites W2157532190 @default.
• W2068695977 cites W2158801409 @default.
• W2068695977 cites W2164389896 @default.
• W2068695977 cites W2166494017 @default.
• W2068695977 cites W2171379946 @default.
• W2068695977 cites W2222530102 @default.
• W2068695977 cites W2241837682 @default.
• W2068695977 cites W2243904500 @default.
• W2068695977 cites W2246304110 @default.
• W2068695977 cites W2246590687 @default.
• W2068695977 cites W2247948724 @default.
• W2068695977 cites W2249967442 @default.
• W2068695977 cites W2250151614 @default.
• W2068695977 cites W2252292203 @default.
• W2068695977 cites W2266708214 @default.
• W2068695977 cites W2281788056 @default.
• W2068695977 cites W2299814273 @default.
• W2068695977 cites W2299873647 @default.
• W2068695977 cites W2401722066 @default.
• W2068695977 cites W2597807083 @default.
• W2068695977 cites W2987227731 @default.
• W2068695977 cites W3159004246 @default.
• W2068695977 cites W3172561670 @default.
• W2068695977 doi "https://doi.org/10.1093/annonc/mds356" @default.
• W2068695977 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22987985" @default.
• W2068695977 hasPublicationYear "2012" @default.
• W2068695977 type Work @default.
• W2068695977 sameAs 2068695977 @default.
• W2068695977 citedByCount "5" @default.
• W2068695977 countsByYear W20686959772012 @default.
• W2068695977 countsByYear W20686959772013 @default.
• W2068695977 countsByYear W20686959772015 @default.
• W2068695977 countsByYear W20686959772019 @default.
• W2068695977 crossrefType "journal-article" @default.

• next