Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Clinical and Translational Challenges in Thyroid Cancer

Author(s): Jorge Hernando*, Javier Ros, Alvaro Arroyo and Jaume Capdevila

Volume 27 , Issue 29 , 2020

Page: [4806 - 4822] Pages: 17

DOI: 10.2174/0929867327666200214125712

Price: $65


Thyroid cancer is the most common endocrine malignancy and it accounts for 1% of all newly diagnosed tumors. Approximately 10% of patients with differentiated thyroid carcinomas (DTC) and 30% with medullary thyroid carcinoma (MTC) could not be cured with locoregional treatment and could develop metastatic disease. In addition, one of the most aggressive solid tumors can arise from the thyroid gland, the anaplastic thyroid carcinoma, with a median overall survival of less than 6 months. Currently, only four drugs are approved for the treatment of DTC and MTC and several unmet needs are focusing the scientific discussions, including the resistant setting, the off-target side effects that may reduce the efficacy and the molecular knowledge-based combinations. In this review, we aimed to discuss the current molecular landscape and treatment of thyroid cancers, and the ongoing clinical and translational research lines focusing on new drugs and drug combinations to improve the inhibition of driver mutations, such as BRAF and RET, and how systemic therapies that improved outcomes of other cancer types, like immunotherapy and peptide receptor radionuclide therapy, may play a role in the future management of advanced thyroid cancers.

Keywords: Thyroid cancer, Multi-Kinase Inhibitors, BRAF mutations, PAX8/PPARγ, RET inhibitors, immunotherapy, clinical trials.

Chen, A.Y.; Jemal, A.; Ward, E.M. Increasing incidence of differentiated thyroid cancer in the United States, 1988-2005. Cancer, 2009, 115(16), 3801-3807.
[] [PMID: 19598221]
Lloyd, R.D.; Osamura, R.V.; Klöppel, G. WHO Classifiation of Tumors of Endocrine Organs, 4th ed; , 2017, Vol. 10, .
Xu, B.; Ghossein, R. Genomic landscape of poorly differentiated and anaplastic thyroid carcinoma. Endocr. Pathol., 2016, 27(3), 205-212.
[] [PMID: 27372303]
Capdevila, J.; Galofré, J.C.; Grande, E.; Zafón Llopis, C.; Ramón, Y. Cajal Asensio, T.; Navarro González, E.; Jiménez-Fonseca, P.; Santamaría Sandi, J.; Gómez Sáez, J.M.; Riesco Eizaguirre, G. Consensus on the management of advanced radioactive iodine-refractory differentiated thyroid cancer on behalf of the Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and Spanish Rare Cancer Working Group (GETHI). Clin. Transl. Oncol., 2017, 19(3), 279-287.
[] [PMID: 27704399]
Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell, 2014, 159(3), 676-690.
[] [PMID: 25417114]
Ciampi, R.; Nikiforov, Y.E. Alterations of the BRAF gene in thyroid tumors. Endocr. Pathol., 2005, 16(3), 163-172.
[] [PMID: 16299399]
Xing, M. BRAF mutation in thyroid cancer. Endocr. Relat. Cancer, 2005, 12(2), 245-262.
[] [PMID: 15947100]
Xing, M.; Westra, W.H.; Tufano, R.P.; Cohen, Y.; Rosenbaum, E.; Rhoden, K.J.; Carson, K.A.; Vasko, V.; Larin, A.; Tallini, G.; Tolaney, S.; Holt, E.H.; Hui, P.; Umbricht, C.B.; Basaria, S.; Ewertz, M.; Tufaro, A.P.; Califano, J.A.; Ringel, M.D.; Zeiger, M.A.; Sidransky, D.; Ladenson, P.W. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J. Clin. Endocrinol. Metab., 2005, 90(12), 6373-6379.
[] [PMID: 16174717]
Suarez, H.G.; du Villard, J.A.; Severino, M.; Caillou, B.; Schlumberger, M.; Tubiana, M.; Parmentier, C.; Monier, R. Presence of mutations in all three ras genes in human thyroid tumors. Oncogene, 1990, 5(4), 565-570.
[PMID: 2183158]
Zhu, Z.; Gandhi, M.; Nikiforova, M.N.; Fischer, A.H.; Nikiforov, Y.E. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am. J. Clin. Pathol., 2003, 120(1), 71-77.
[] [PMID: 12866375]
Shi, Y.F.; Zou, M.J.; Schmidt, H.; Juhasz, F.; Stensky, V.; Robb, D.; Farid, N.R. High rates of ras codon 61 mutation in thyroid tumors in an iodide-deficient area. Cancer Res., 1991, 51(10), 2690-2693.
[PMID: 2021946]
Nikiforova, M.N.; Wald, A.I.; Roy, S.; Durso, M.B.; Nikiforov, Y.E. Targeted next-generation sequencing panel (ThyroSeq) for detection of mutations in thyroid cancer. J. Clin. Endocrinol. Metab., 2013, 98(11), E1852-E1860.
[] [PMID: 23979959]
Tallini, G.; Asa, S.L. RET oncogene activation in papillary thyroid carcinoma. Adv. Anat. Pathol., 2001, 8(6), 345-354.
[] [PMID: 11707626]
Romei, C.; Ciampi, R.; Casella, F.; Tacito, A.; Torregrossa, L.; Ugolini, C.; Basolo, F.; Materazzi, G.; Vitti, P.; Elisei, R. RET mutation heterogeneity in primary advanced medullary thyroid cancers and their metastases. Oncotarget, 2018, 9(11), 9875-9884.
[] [PMID: 29515777]
Reddi, H.V.; McIver, B.; Grebe, S.K.; Eberhardt, N.L. The paired box-8/peroxisome proliferator-activated receptor-gamma oncogene in thyroid tumorigenesis. Endocrinology, 2007, 148(3), 932-935.
[] [PMID: 16946003]
Liu, X.; Bishop, J.; Shan, Y.; Pai, S.; Liu, D.; Murugan, A.K.; Sun, H.; El-Naggar, A.K.; Xing, M. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr. Relat. Cancer, 2013, 20(4), 603-610.
[] [PMID: 23766237]
Landa, I.; Ganly, I.; Chan, T.A.; Mitsutake, N.; Matsuse, M.; Ibrahimpasic, T.; Ghossein, R.A.; Fagin, J.A. Frequent somatic TERT promoter mutations in thyroid cancer: higher prevalence in advanced forms of the disease. J. Clin. Endocrinol. Metab., 2013, 98(9), E1562-E1566.
[] [PMID: 23833040]
Xing, M. Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer. Thyroid, 2010, 20(7), 697-706.
[] [PMID: 20578891]
Levine, A.J.; Oren, M. The first 30 years of p53: growing ever more complex. Nat. Rev. Cancer, 2009, 9(10), 749-758.
[] [PMID: 19776744]
Brose, M.S.; Nutting, C.M.; Jarzab, B. Sorafenib in locally advanced or metastatic, radioactive iodine-refractory, differentiated thyroid cancer: a randomized, double-blind, phase 3 trial. Lancer, 2014, 384(9940), 319-328.
[] [PMID: 24768112]
Jaume, Capdevil; Ignacio Matos, Garcia Francesco M Mancuso, Carmela Iglesias, Paolo Nuciforo, Carles Zafon, Hector G. Palmer, Zighereda Ogbah, Laura Muiños, Carol Elaine Pena, Marcia S. Brose, Martin Schlumberger, Ana Vivancos. RNAseq analysis of the sorafenib phase III DECISION trial in differentiated thyroid cancer (DTC): Correlation with clinical outcome. J. Clin. Oncol., 2017, 35(15_suppl), 6083-6083.
Matos, I; Mancuso, F; Iglesias, C. Prognostic impact of RNA expression profile (EP) in the phase III DECISION trial for patients with advanced radioactive-iodine refractory differentiated thyroid cancer (DTC). Ann Oncol, 2017, 28(Issue suppl_5)
Bowles, DW; Ross, JS; Gay, LM Comprehensive genomic profiling of anaplastic thyroid carcinoma. J Clin Oncol, 2018, 36(suppl;abstr 6089)
Capdevila, J.; Mayor, R.; Mancuso, F.M.; Iglesias, C.; Caratù, G.; Matos, I.; Zafón, C.; Hernando, J.; Petit, A.; Nuciforo, P.; Cameselle-Teijeiro, J.M.; Álvarez, C.; Recio, J.A.; Tabernero, J.; Matias-Guiu, X.; Vivancos, A.; Seoane, J. Early evolutionary divergence between papillary and anaplastic thyroid cancers. Ann. Oncol., 2018, 29(6), 1454-1460.
[] [PMID: 29648575]
Schlumberger, M.; Tahara, M.; Wirth, L.J.; Robinson, B.; Brose, M.S.; Elisei, R.; Habra, M.A.; Newbold, K.; Shah, M.H.; Hoff, A.O.; Gianoukakis, A.G.; Kiyota, N.; Taylor, M.H.; Kim, S.B.; Krzyzanowska, M.K.; Dutcus, C.E.; de las Heras, B.; Zhu, J.; Sherman, S.I. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N. Engl. J. Med., 2015, 372(7), 621-630.
[] [PMID: 25671254]
Wells, S.A., Jr; Robinson, B.G.; Gagel, R.F.; Dralle, H.; Fagin, J.A.; Santoro, M.; Baudin, E.; Elisei, R.; Jarzab, B.; Vasselli, J.R.; Read, J.; Langmuir, P.; Ryan, A.J.; Schlumberger, M.J. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J. Clin. Oncol., 2012, 30(2), 134-141.
[] [PMID: 22025146]
Elisei, R.; Schlumberger, M.J.; Müller, S.P.; Schöffski, P.; Brose, M.S.; Shah, M.H.; Licitra, L.; Jarzab, B.; Medvedev, V.; Kreissl, M.C.; Niederle, B.; Cohen, E.E.; Wirth, L.J.; Ali, H.; Hessel, C.; Yaron, Y.; Ball, D.; Nelkin, B.; Sherman, S.I. Cabozantinib in progressive medullary thyroid cancer. J. Clin. Oncol., 2013, 31(29), 3639-3646.
[] [PMID: 24002501]
Cohen, E.E.; Rosen, L.S.; Vokes, E.E.; Kies, M.S.; Forastiere, A.A.; Worden, F.P.; Kane, M.A.; Sherman, E.; Kim, S.; Bycott, P.; Tortorici, M.; Shalinsky, D.R.; Liau, K.F.; Cohen, R.B. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J. Clin. Oncol., 2008, 26(29), 4708-4713.
[] [PMID: 18541897]
Sherman, S.I.; Wirth, L.J.; Droz, J.P.; Hofmann, M.; Bastholt, L.; Martins, R.G.; Licitra, L.; Eschenberg, M.J.; Sun, Y.N.; Juan, T.; Stepan, D.E.; Schlumberger, M.J. Motesanib Thyroid Cancer Study Group. Motesanib diphosphate in progressive differentiated thyroid cancer. N. Engl. J. Med., 2008, 359(1), 31-42.
[] [PMID: 18596272]
Carr, L.L.; Mankoff, D.A.; Goulart, B.H.; Eaton, K.D.; Capell, P.T.; Kell, E.M.; Bauman, J.E.; Martins, R.G. 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(21), 5260-5268.
[] [PMID: 20847059]
Ravaud, A.; de la Fouchardière, C.; Caron, P.; Doussau, A.; Do Cao, C.; Asselineau, J.; Rodien, P.; Pouessel, D.; Nicolli-Sire, P.; Klein, M.; Bournaud-Salinas, C.; Wemeau, J.L.; Gimbert, A.; Picat, M.Q.; Pedenon, D.; Digue, L.; Daste, A.; Catargi, B.; Delord, J.P. A multicenter phase II study of sunitinib in patients with locally advanced or metastatic differentiated, anaplastic or medullary thyroid carcinomas: mature data from the THYSU study. Eur. J. Cancer, 2017, 76, 110-117.
[] [PMID: 28301826]
Bible, K.C.; Suman, V.J.; Molina, J.R.; Smallridge, R.C.; Maples, W.J.; Menefee, M.E.; Rubin, J.; Sideras, K.; Morris, J.C., III; McIver, B.; Burton, J.K.; Webster, K.P.; Bieber, C.; Traynor, A.M.; Flynn, P.J.; Goh, B.C.; Tang, H.; Ivy, S.P.; Erlichman, C. Endocrine Malignancies Disease Oriented Group. Mayo Clinic Cancer Center; Mayo Phase 2 Consortium. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol., 2010, 11(10), 962-972.
[] [PMID: 20851682]
Bible, K.C.; Suman, V.J.; Molina, J.R.; Smallridge, R.C.; Maples, W.J.; Menefee, M.E.; Rubin, J.; Karlin, N.; Sideras, K.; Morris, J.C., III; McIver, B.; Hay, I.; Fatourechi, V.; Burton, J.K.; Webster, K.P.; Bieber, C.; Traynor, A.M.; Flynn, P.J.; Cher Goh, B.; Isham, C.R.; Harris, P.; Erlichman, C. Endocrine Malignancies Disease Oriented Group. Mayo Clinic Cancer Center, and the Mayo Phase 2 Consortium. A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H. J. Clin. Endocrinol. Metab., 2014, 99(5), 1687-1693.
[] [PMID: 24606083]
Lim, S.M.; Chung, W.Y.; Nam, K.H.; Kang, S.W.; Lim, J.Y.; Kim, H.G.; Shin, S.H.; Sun, J.M.; Kim, S.G.; Kim, J.H.; Kang, C.W.; Kim, H.R.; Cho, B.C. An open label, multicenter, phase II study of dovitinib in advanced thyroid cancer. Eur. J. Cancer, 2015, 51(12), 1588-1595.
[] [PMID: 26070683]
Schlumberger, M; Newbold, K; Hasan, B A randomized doubled blind phase II study exploring the safety and efficacy of nintedanib (BIBF1120) as second line therapy for patients (pts) with differentiated thyroid carcinoma (CTD) progressing after first line therapy: EORTC 1209. J Clin Oncol., 2018, 36(suppl; abstr 6021)
Brose, MS; Shenoy, S; Bhat, N A phase II trial of cabozantinib (CABO) for the treatment of radioiodine (RAI)-refractory differentiated thyroid carcinoma (DTC) in the first-line setting. J Clin Oncol., 2018, 36(suppl; abstr 6088)
Cabanillas, M.E.; de Souza, J.A.; Geyer, S.; Wirth, L.J.; Menefee, M.E.; Liu, S.V.; Shah, K.; Wright, J.; Shah, M.H. Cabozantinib as salvage therapy for patients with tyrosine kinase inhibitor-refractory differentiated thyroid cancer: Results of a multicenter phase II international thyroid oncology group trial. J. Clin. Oncol., 2017, 35(29), 3315-3321.
[] [PMID: 28817373]
Schlumberger, M.; Jarzab, B.; Cabanillas, M.E.; Robinson, B.; Pacini, F.; Ball, D.W.; McCaffrey, J.; Newbold, K.; Allison, R.; Martins, R.G.; Licitra, L.F.; Shah, M.H.; Bodenner, D.; Elisei, R.; Burmeister, L.; Funahashi, Y.; Ren, M.; O’Brien, J.P.; Sherman, S.I. A phase II trial of the multitarget thyrosine kinase inhibitor Lenvatinib (E7080) in advanced medullary thyroid cancer. Clin. Cancer Res., 2016, 22(1), 44-53.
[] [PMID: 26311725]
Ito, Y.; Onoda, N. Ito, KI Sorafenib in Japanese patients with locally advanced or metastatic medullary thyroid carcinoma and anaplastic thyroid carcinoma. Thyroid, 2017, 27(9), 1142-1148.
Tahara, M.; Kiyota, N.; Yamazaki, T.; Chayahara, N.; Nakano, K.; Inagaki, L.; Toda, K.; Enokida, T.; Minami, H.; Imamura, Y.; Sasaki, T.; Suzuki, T.; Fujino, K.; Dutcus, C.E.; Takahashi, S. Lenvatinib for Anaplastic Thyroid Cancer. Front. Oncol., 2017, 7, 25.
[] [PMID: 28299283]
Wan, P.T.; Garnett, M.J.; Roe, S.M.; Lee, S.; Niculescu-Duvaz, D.; Good, V.M.; Jones, C.M.; Marshall, C.J.; Springer, C.J.; Barford, D.; Marais, R. Cancer Genome Project. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell, 2004, 116(6), 855-867.
[] [PMID: 15035987]
Hou, P.; Liu, D.; Xing, M. Functional characterization of the T1799-1801del and A1799-1816ins BRAF mutations in papillary thyroid cancer. Cell Cycle, 2007, 6(3), 377-379.
[] [PMID: 17297294]
Trovisco, V.; Soares, P.; Preto, A.; de Castro, I.V.; Lima, J.; Castro, P.; Máximo, V.; Botelho, T.; Moreira, S.; Meireles, A.M.; Magalhães, J.; Abrosimov, A.; Cameselle-Teijeiro, J.; Sobrinho-Simões, M. Type and prevalence of BRAF mutations are closely associated with papillary thyroid carcinoma histotype and patients’ age but not with tumour aggressiveness. Virchows Arch., 2005, 446(6), 589-595.
[] [PMID: 15902486]
Afkhami, M.; Karunamurthy, A.; Chiosea, S.; Nikiforova, M.N.; Seethala, R.; Nikiforov, Y.E.; Coyne, C. Histopathologic and Clinical Characterization of Thyroid Tumors Carrying the BRAF(K601E) Mutation. Thyroid, 2016, 26(2), 242-247.
[] [PMID: 26422023]
Trovisco, V.; Vieira de Castro, I.; Soares, P.; Máximo, V.; Silva, P.; Magalhães, J.; Abrosimov, A.; Guiu, X.M.; Sobrinho-Simões, M. BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J. Pathol., 2004, 202(2), 247-251.
[] [PMID: 14743508]
Ciampi, R.; Knauf, J.A.; Kerler, R.; Gandhi, M.; Zhu, Z.; Nikiforova, M.N.; Rabes, H.M.; Fagin, J.A.; Nikiforov, Y.E. Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer. J. Clin. Invest., 2005, 115(1), 94-101.
[] [PMID: 15630448]
Nikiforova, M.N.; Kimura, E.T.; Gandhi, M.; Biddinger, P.W.; Knauf, J.A.; Basolo, F.; Zhu, Z.; Giannini, R.; Salvatore, G.; Fusco, A.; Santoro, M.; Fagin, J.A.; Nikiforov, Y.E. 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(11), 5399-5404.
[] [PMID: 14602780]
Adeniran, A.J.; Zhu, Z.; Gandhi, M.; Steward, D.L.; Fidler, J.P.; Giordano, T.J.; Biddinger, P.W.; Nikiforov, Y.E. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am. J. Surg. Pathol., 2006, 30(2), 216-222.
[] [PMID: 16434896]
Kim, T.Y.; Kim, W.B.; Rhee, Y.S.; Song, J.Y.; Kim, J.M.; Gong, G.; Lee, S.; Kim, S.Y.; Kim, S.C.; Hong, S.J.; Shong, Y.K. The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma. Clin. Endocrinol. (Oxf.), 2006, 65(3), 364-368.
[] [PMID: 16918957]
Fagin, J.A.; Wells, S.A., Jr Biologic and Clinical Perspectives on Thyroid Cancer. N. Engl. J. Med., 2016, 375(11), 1054-1067.
[] [PMID: 27626519]
Falchook, G.S.; Millward, M.; Hong, D.; Naing, A.; Piha-Paul, S.; Waguespack, S.G.; Cabanillas, M.E.; Sherman, S.I.; Ma, B.; Curtis, M.; Goodman, V.; Kurzrock, R. BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer. Thyroid, 2015, 25(1), 71-77.
[] [PMID: 25285888]
Brose, M.S.; Cabanillas, M.E.; Cohen, E.E.; Wirth, L.J.; Riehl, T.; Yue, H.; Sherman, S.I.; Sherman, E.J. Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial. Lancet Oncol., 2016, 17(9), 1272-1282.
[] [PMID: 27460442]
Manisha, S.H.; Wei, L.; Wirth, L.J. Results of randomized phase 2 trial of dabrafenib versus dabrefenib plus trametinib in BRAF-mutated papillary thyroid carcinoma. J. Clin. Oncol., 2017, 35(15 suppl), 6022-6022.
Subbiah, V.; Kreitman, R.J.; Wainberg, Z.A.; Cho, J.Y.; Schellens, J.H.M.; Soria, J.C.; Wen, P.Y.; Zielinski, C.; Cabanillas, M.E.; Urbanowitz, G.; Mookerjee, B.; Wang, D.; Rangwala, F.; Keam, B. Dabrafenib and Trametinib treatment in patients with locally advanced or metastatic BRAF B600-mutant anaplastic thyroid cancer. J. Clin. Oncol., 2018, 36(1), 7-13.
[] [PMID: 29072975]
Huang, F.W.; Hodis, E.; Xu, M.J.; Kryukov, G.V.; Chin, L.; Garraway, L.A. Highly recurrent TERT promoter mutations in human melanoma. Science, 2013, 339(6122), 957-959.
[] [PMID: 23348506]
Xing, M.; Liu, R.; Liu, X. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J. Clin. Oncol., 2014, 32(25), 2718-2726.
Jäger, K.; Walter, M. Therapeutic targeting of telomerase. Genes (Basel), 2016, 7(7), E39.
[] [PMID: 27455328]
Teng, L.; Specht, M.C.; Barden, C.B.; Fahey, T.J. III Antisense hTERT inhibits thyroid cancer cell growth. J. Clin. Endocrinol. Metab., 2003, 88(3), 1362-1366.
[] [PMID: 12629130]
Maggisano, V.; Celano, M.; Lombardo, G.E.; Lepore, S.M.; Sponziello, M.; Rosignolo, F.; Verrienti, A.; Baldan, F.; Puxeddu, E.; Durante, C.; Filetti, S.; Damante, G.; Russo, D.; Bulotta, S. Silencing of hTERT blocks growth and migration of anaplastic thyroid cancer cells. Mol. Cell. Endocrinol., 2017, 448, 34-40.
[] [PMID: 28288903]
Rimawi, M.F.; Schiff, R.; Osborne, C.K. Targeting HER2 for the treatment of breast cancer. Annu. Rev. Med., 2015, 66, 111-128.
[] [PMID: 25587647]
Montero-Conde, C.; Ruiz-Llorente, S.; Dominguez, J.M.; Knauf, J.A.; Viale, A.; Sherman, E.J.; Ryder, M.; Ghossein, R.A.; Rosen, N.; Fagin, J.A. Relief of feedback inhibition of HER3 tanscription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF-mutant thyroid carcinomas. Cancer Discov., 2013, 3(5), 520-533.
[] [PMID: 23365119]
Sherman, EJ; Ho, AL Fagin JA Combination of dabrafenib (DAB) and lapatinib (LAP) for the treatment of BRAFmutant thyroid cancer. J Clin Oncol, 2018, 36(suppl;abstr 6087)
Kroll, T.G.; Sarraf, P.; Pecciarini, L.; Chen, C.J.; Mueller, E.; Spiegelman, B.M.; Fletcher, J.A. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected] Science, 2000, 289(5483), 1357-1360.
[] [PMID: 10958784]
Eberhardt, N.L.; Grebe, S.K.; McIver, B.; Reddi, H.V. The role of the PAX8/PPARgamma fusion oncogene in the pathogenesis of follicular thyroid cancer. Mol. Cell. Endocrinol., 2010, 321(1), 50-56.
[] [PMID: 19883731]
French, C.A.; Alexander, E.K.; Cibas, E.S.; Nose, V.; Laguette, J.; Faquin, W.; Garber, J.; Moore, F., Jr; Fletcher, J.A.; Larsen, P.R.; Kroll, T.G. Genetic and biological subgroups of low-stage follicular thyroid cancer. Am. J. Pathol., 2003, 162(4), 1053-1060.
[] [PMID: 12651598]
Dwight, T.; Thoppe, S.E.R.; Foukakis, T. Genetic and biological subgroups of low-stage follicular thyroid cancer. Am J Endorcinol Metabol, 2003, 88, 4440-4445.
Placzkowski, K.A.; Reddi, H.V.; Grebe, S.K.; Eberhardt, N.L.; McIver, B. The role of the PAX8/PPAR γ fusion oncogene in thyroid cancer. PPAR Res., 2008, Article ID 672829.
[] [PMID: 18989374]
Presta, I.; Arturi, F.; Ferretti, E.; Mattei, T.; Scarpelli, D.; Tosi, E.; Scipioni, A.; Celano, M.; Gulino, A.; Filetti, S.; Russo, D. Recovery of NIS expression in thyroid cancer cells by overexpression of Pax8 gene. BMC Cancer, 2005, 5, 80.
[] [PMID: 16029487]
Kebebew, E.; Peng, M.; Reiff, E.; Treseler, P.; Woeber, K.A.; Clark, O.H.; Greenspan, F.S.; Lindsay, S.; Duh, Q.Y.; Morita, E. A phase II trial of rosiglitazone in patients with thyroglobulin-positive and radioiodine-negative differentiated thyroid cancer. Surgery, 2006, 140(6), 960-966.
[] [PMID: 17188145]
Tepmongkol, S.; Keelawat, S.; Honsawek, S.; Ruangvejvorachai, P. Rosiglitazone effect on radioiodine uptake in thyroid carcinoma patients with high thyroglobulin but negative total body scan: a correlation with the expression of peroxisome proliferator-activated receptor-gamma. Thyroid, 2008, 18(7), 697-704.
[] [PMID: 18630997]
Giordano, T.J.; Haugen, B.R.; Sherman, S.I.; Shah, M.H.; Caoili, E.M.; Koenig, R.J. Pioglitazone therapy of PAX8-PPARγ Fusion protein thyroid carcinoma. J. Clin. Endocrinol. Metab., 2018, 103(4), 1277-1281.
[] [PMID: 29373711]
Xing, M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr. Rev., 2007, 28(7), 742-762.
[] [PMID: 17940185]
Riesco-Eizaguirre, G.; Gutiérrez-Martínez, P.; García-Cabezas, M.A.; Nistal, M.; Santisteban, P. The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I- targeting to the membrane. Endocr. Relat. Cancer, 2006, 13(1), 257-269.
[] [PMID: 16601293]
Barollo, S.; Pennelli, G.; Vianello, F.; Watutantrige Fernando, S.; Negro, I.; Merante Boschin, I.; Pelizzo, M.R.; Rugge, M.; Mantero, F.; Nacamulli, D.; Girelli, M.E.; Busnardo, B.; Mian, C. BRAF in primary and recurrent papillary thyroid cancers: the relationship with (131)I and 2-[(18)F]fluoro-2-deoxy-D-glucose uptake ability. Eur. J. Endocrinol., 2010, 163(4), 659-663.
[] [PMID: 20647301]
Giordano, T.J.; Kuick, R.; Thomas, D.G.; Misek, D.E.; Vinco, M.; Sanders, D.; Zhu, Z.; Ciampi, R.; Roh, M.; Shedden, K.; Gauger, P.; Doherty, G.; Thompson, N.W.; Hanash, S.; Koenig, R.J.; Nikiforov, Y.E. Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis. Oncogene, 2005, 24(44), 6646-6656.
[] [PMID: 16007166]
Mian, C.; Barollo, S.; Pennelli, G.; Pavan, N.; Rugge, M.; Pelizzo, M.R.; Mazzarotto, R.; Casara, D.; Nacamulli, D.; Mantero, F.; Opocher, G.; Busnardo, B.; Girelli, M.E. Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake. Clin. Endocrinol. (Oxf.), 2008, 68(1), 108-116.
[] [PMID: 17854396]
Durante, C.; Puxeddu, E.; Ferretti, E.; Morisi, R.; Moretti, S.; Bruno, R.; Barbi, F.; Avenia, N.; Scipioni, A.; Verrienti, A.; Tosi, E.; Cavaliere, A.; Gulino, A.; Filetti, S.; Russo, D. BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism. J. Clin. Endocrinol. Metab., 2007, 92(7), 2840-2843.
[] [PMID: 17488796]
Rothenberg, SM; McFadden, DG Palmer, EL Redifferentiation of Iodine-Refractory BRAF V600E-Mutant Metastatic Papillary Thyroid Cancer with Dabrafenib. Clin Cancer Res., 2015. 1March; 21 (5), 1028-1035
Huillard, O.; Tenenbaum, F.; Clerc, J.; Goldwasser, F.; Groussin, L. Restoring radioiodine uptake in BRAF V600E-mutated papillary thyroid cancer. J. Endocr. Soc., 2017, 1(4), 285-287.
[] [PMID: 29264486]
Ho, A.L.; Grewal, R.K.; Leboeuf, R.; Sherman, E.J.; Pfister, D.G.; Deandreis, D.; Pentlow, K.S.; Zanzonico, P.B.; Haque, S.; Gavane, S.; Ghossein, R.A.; Ricarte-Filho, J.C.; Domínguez, J.M.; Shen, R.; Tuttle, R.M.; Larson, S.M.; Fagin, J.A. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N. Engl. J. Med., 2013, 368(7), 623-632.
[] [PMID: 23406027]
Tallini, G.; Santoro, M.; Helie, M.; Carlomagno, F.; Salvatore, G.; Chiappetta, G.; Carcangiu, M.L.; Fusco, A. RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. Clin. Cancer Res., 1998, 4(2), 287-294.
[PMID: 9516913]
Ciampi, R.; Nikiforov, Y.E. RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis. Endocrinology, 2007, 148(3), 936-941.
[] [PMID: 16946010]
Sapio, M.R.; Guerra, A.; Marotta, V.; Campanile, E.; Formisano, R.; Deandrea, M.; Motta, M.; Limone, P.P.; Fenzi, G.; Rossi, G.; Vitale, M. High growth rate of benign thyroid nodules bearing RET/PTC rearrangements. J. Clin. Endocrinol. Metab., 2011, 96(6), E916-E919.
[] [PMID: 21411555]
Marotta, V.; Guerra, A.; Sapio, M.R.; Vitale, M. RET/PTC rearrangement in benign and malignant thyroid diseases: a clinical standpoint. Eur. J. Endocrinol., 2011, 165(4), 499-507.
[] [PMID: 21750045]
Castellone, M.D.; De Falco, V.; Rao, D.M.; Bellelli, R.; Muthu, M.; Basolo, F.; Fusco, A.; Gutkind, J.S.; Santoro, M. The β-catenin axis integrates multiple signals downstream from RET/papillary thyroid carcinoma leading to cell proliferation. Cancer Res., 2009, 69(5), 1867-1876.
[] [PMID: 19223551]
Miyagi, E.; Braga-Basaria, M.; Hardy, E.; Vasko, V.; Burman, K.D.; Jhiang, S.; Saji, M.; Ringel, M.D. Chronic expression of RET/PTC 3 enhances basal and insulin-stimulated PI3 kinase/AKT signaling and increases IRS-2 expression in FRTL-5 thyroid cells. Mol. Carcinog., 2004, 41(2), 98-107.
[] [PMID: 15378648]
Saenko, V.; Rogounovitch, T.; Shimizu-Yoshida, Y.; Abrosimov, A.; Lushnikov, E.; Roumiantsev, P.; Matsumoto, N.; Nakashima, M.; Meirmanov, S.; Ohtsuru, A.; Namba, H.; Tsyb, A.; Yamashita, S. Novel tumorigenic rearrangement, Delta rfp/ret, in a papillary thyroid carcinoma from externally irradiated patient. Mutat. Res., 2003, 527(1-2), 81-90.
[] [PMID: 12787916]
Rabes, H.M.; Demidchik, E.P.; Sidorow, J.D.; Lengfelder, E.; Beimfohr, C.; Hoelzel, D.; Klugbauer, S. 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(3), 1093-1103.
[PMID: 10741739]
Opsahl, E.M.; Brauckhoff, M.; Schlichting, E.; Helset, K.; Svartberg, J.; Brauckhoff, K.; Mæhle, L.; Engebretsen, L.F.; Sigstad, E.; Grøholt, K.K.; Akslen, L.A.; Jørgensen, L.H.; Varhaug, J.E.; Bjøro, T. A Nationwide Study of Multiple Endocrine Neoplasia Type 2A in Norway: Predictive and Prognostic Factors for the Clinical Course of Medullary Thyroid Carcinoma. Thyroid, 2016, 26(9), 1225-1238.
[] [PMID: 27400880]
Elisei, R.; Cosci, B.; Romei, C.; Bottici, V.; Renzini, G.; Molinaro, E.; Agate, L.; Vivaldi, A.; Faviana, P.; Basolo, F.; Miccoli, P.; Berti, P.; Pacini, F.; Pinchera, A. Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J. Clin. Endocrinol. Metab., 2008, 93(3), 682-687.
[] [PMID: 18073307]
Seoane, J.; Capdevila, J. The right compound for the right target: tackling RET. Ann. Oncol., 2018, 29(8), 1623-1625.
[] [PMID: 29860429]
Subbiah, V.; Gainor, J.F.; Rahal, R.; Brubaker, J.D.; Kim, J.L.; Maynard, M.; Hu, W.; Cao, Q.; Sheets, M.P.; Wilson, D.; Wilson, K.J.; DiPietro, L.; Fleming, P.; Palmer, M.; Hu, M.I.; Wirth, L.; Brose, M.S.; Ou, S.I.; Taylor, M.; Garralda, E.; Miller, S.; Wolf, B.; Lengauer, C.; Guzi, T.; Evans, E.K. Precision Targeted Therapy with BLU-667 for RET-Driven Cancers. Cancer Discov., 2018, 8(7), 836-849.
[] [PMID: 29657135]
Subbiah, V.; Taylor, M.; Lin, J. Highly potent and selective RET inhibitor, BLU-667, achieves proof of concept in a phase I study of advanced, RET-altered solid tumors. AACR Annual Meeting. Abstract CT043., 2018. Presented April 15, 2018.
Subbiah, V.; Velcheti, V.; Tuch, B.B.; Ebata, K.; Busaidy, N.L.; Cabanillas, M.E.; Wirth, L.J.; Stock, S.; Smith, S.; Lauriault, V.; Corsi-Travali, S.; Henry, D.; Burkard, M.; Hamor, R.; Bouhana, K.; Winski, S.; Wallace, R.D.; Hartley, D.; Rhodes, S.; Reddy, M.; Brandhuber, B.J.; Andrews, S.; Rothenberg, S.M.; Drilon, A. Selective RET kinase inhibition for patients with RET-altered cancers. Ann. Oncol., 2018, 29(8), 1869-1876.
[] [PMID: 29912274]
Drilon, AE; Subbiah, V; Oxnard, GR A phase 1 study of LOXO-292, a potent and highly selective RET inhibitor, in patients with RET-altered cancers. J Clin Oncol., 2018, 36(suppl; abstr 102)
García-Rostán, G.; Costa, A.M.; Pereira-Castro, I.; Salvatore, G.; Hernandez, R.; Hermsem, M.J.; Herrero, A.; Fusco, A.; Cameselle-Teijeiro, J.; Santoro, M. Mutation of the PIK3CA gene in anaplastic thyroid cancer. Cancer Res., 2005, 65(22), 10199-10207.
[] [PMID: 16288007]
Abubaker, J.; Jehan, Z.; Bavi, P.; Sultana, M.; Al-Harbi, S.; Ibrahim, M.; Al-Nuaim, A.; Ahmed, M.; Amin, T.; Al-Fehaily, M.; Al-Sanea, O.; Al-Dayel, F.; Uddin, S.; Al-Kuraya, K.S. Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population. J. Clin. Endocrinol. Metab., 2008, 93(2), 611-618.
[] [PMID: 18000091]
Liu, Z.; Hou, P.; Ji, M.; Guan, H.; Studeman, K.; Jensen, K.; Vasko, V.; El-Naggar, A.K.; Xing, M. Highly prevalent genetic alterations in receptor tyrosine kinases and phosphatidylinositol 3-kinase/akt and mitogen-activated protein kinase pathways in anaplastic and follicular thyroid cancers. J. Clin. Endocrinol. Metab., 2008, 93(8), 3106-3116.
[] [PMID: 18492751]
Schneider, T.C.; de Wit, D.; Links, T.P. Everolimus in patients with advanced follicular-derived thyroid cancer. J. Clin. Endocrinol. Metab., 2017, 102(2), 698-707.
Sherman, EJ; Ho, AL; Fury, SS Combination of everolimus and sorafenib in the treatment of thyroid cancer. Update of the phase II study. J Clin Oncol, 2015, 33(suppl; abstr 6069)
Reubi, J.C.; Schaer, J.C.; Waser, B.; Mengod, G. Expression and localization of somatostatin receptor SSTR1, SSTR2, and SSTR3 messenger RNAs in primary human tumors using in situ hybridization. Cancer Res., 1994, 54(13), 3455-3459.
[PMID: 8012966]
Iten, F.; Müller, B.; Schindler, C.; Rochlitz, C.; Oertli, D.; Mäcke, H.R.; Müller-Brand, J.; Walter, M.A. Response to [90Yttrium-DOTA]-TOC treatment is associated with long-term survival benefit in metastasized medullary thyroid cancer: a phase II clinical trial. Clin. Cancer Res., 2007, 13(22 Pt 1), 6696-6702.
[] [PMID: 18006770]
Salavati, A.; Puranik, A.; Kulkarni, H.R.; Budiawan, H.; Baum, R.P. Peptide Receptor Radionuclide Therapy (PRRT) of medullary and no medullary thyroid cancer using radiolabeled somatostatin analogues. Semin. Nucl. Med., 2016, 46(3), 215-224.
[] [PMID: 27067502]
Bläker, M.; de Weerth, A.; Tometten, M.; Schulz, M.; Höppner, W.; Arlt, D.; Hoang-Vu, C.; Dralle, H.; Terpe, H.; Jonas, L.; von Schrenck, T. Expression of the cholecystokinin 2-receptor in normal human thyroid gland and medullary thyroid carcinoma. Eur. J. Endocrinol., 2002, 146(1), 89-96.
[] [PMID: 11751073]
Rottenburger, C; Nicolas, G; McDougall, L Title evaluation of the CCK-2-receptor agonist 177Lu-PP-F1N for peptide receptor radionuclide therapy (PRRT) of medullary thyroid carcinoma – First results of a phase 0 ‘Lumed’ Study. Endoc Abstr, 2018, 56(GP234)
Le, D.T.; Uram, J.N.; Wang, H.; Bartlett, B.R.; Kemberling, H.; Eyring, A.D.; Skora, A.D.; Luber, B.S.; Azad, N.S.; Laheru, D.; Biedrzycki, B.; Donehower, R.C.; Zaheer, A.; Fisher, G.A.; Crocenzi, T.S.; Lee, J.J.; Duffy, S.M.; Goldberg, R.M.; de la Chapelle, A.; Koshiji, M.; Bhaijee, F.; Huebner, T.; Hruban, R.H.; Wood, L.D.; Cuka, N.; Pardoll, D.M.; Papadopoulos, N.; Kinzler, K.W.; Zhou, S.; Cornish, T.C.; Taube, J.M.; Anders, R.A.; Eshleman, J.R.; Vogelstein, B.; Diaz, L.A., Jr PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med., 2015, 372(26), 2509-2520.
[] [PMID: 26028255]
Ahn, S.; Kim, T.H.; Kim, S.W.; Ki, C.S.; Jang, H.W.; Kim, J.S.; Kim, J.H.; Choe, J.H.; Shin, J.H.; Hahn, S.Y.; Oh, Y.L.; Chung, J.H. Comprehensive screening for PD-L1 expression in thyroid cancer. Endocr. Relat. Cancer, 2017, 24(2), 97-106.
[] [PMID: 28093480]
Mehnert, JM; Varga, A Marcia Brose, M Pembrolizumab for advanced papillary or follicular thyroid cancer: preliminary results from the phase 1b KEYNOTE-028 study. J Clin Oncol, 2016, 34(suppl; abstr 6091)
Bastman, J.J.; Serracino, H.S.; Zhu, Y.; Koenig, M.R.; Mateescu, V.; Sams, S.B.; Davies, K.D.; Raeburn, C.D.; McIntyre, R.C., Jr; Haugen, B.R.; French, J.D.; Tumor-Infiltrating, T. Cells and the PD-1 checkpoint pathway in advanced differentiated and anaplastic thyroid cancer. J. Clin. Endocrinol. Metab., 2016, 101(7), 2863-2873.
[] [PMID: 27045886]
Wirth, LJ; Eigendorff, E; Capdevila, J Phase I/II study of spartalizumab (PDR001), an anti-PD1 mAb, in patients with anaplastic thyroid cancer. J Clin Oncol., 2018, 36(suppl; abstr 6024)
Terme, M.; Pernot, S.; Marcheteau, E.; Sandoval, F.; Benhamouda, N.; Colussi, O.; Dubreuil, O.; Carpentier, A.F.; Tartour, E.; Taieb, J. VEGFA-VEGFR pathway blockade inhibits tumor-induced regulatory T-cell proliferation in colorectal cancer. Cancer Res., 2013, 73(2), 539-549.
[] [PMID: 23108136]
Angell, T.E.; Lechner, M.G.; Jang, J.K.; Correa, A.J.; LoPresti, J.S.; Epstein, A.L. BRAF V600E in papillary thyroid carcinoma is associated with increased programmed death ligand 1 expression and suppressive immune cell infiltration. Thyroid, 2014, 24(9), 1385-1393.
[] [PMID: 24955518]
Iyer, P.C.; Dadu, R.; Gule-Monroe, M.; Busaidy, N.L.; Ferrarotto, R.; Habra, M.A.; Zafereo, M.; Williams, M.D.; Gunn, G.B.; Grosu, H.; Skinner, H.D.; Sturgis, E.M.; Gross, N.; Cabanillas, M.E. Salvage pembrolizumab added to kinase inhibitor therapy for the treatment of anaplastic thyroid carcinoma. J. Immunother. Cancer, 2018, 6(1), 68.
[] [PMID: 29996921]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy