Publication Cover
Expert Review of Precision Medicine and Drug Development
Personalized medicine in drug development and clinical practice
Volume 4, 2019 - Issue 1
112
Views
4
CrossRef citations to date
0
Altmetric
Review

Recent advances in precision medicine for the treatment of anaplastic thyroid cancer

, , , , , , , , & show all
Pages 37-49 | Received 31 Oct 2018, Accepted 02 Jan 2019, Published online: 09 Jan 2019

References

  • American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19(11):1167–1214.
  • Key statistics for thyroid cancer. american cancer society. Available from: https://www.cancer.org/cancer/thyroid-cancer/about/key-statistics.html. [cited October 2018]
  • Cancer Facts & Figures. American cancer society. Atlanta: American Cancer Society; 2016.
  • Sherman SI. Thyroid carcinoma. Lancet. 2003;361(9356):501–511.
  • Fallahi P, Ferrari SM, Baldini E, et al. The safety and efficacy of vandetanib in the treatment of progressive medullary thyroid cancer. Expert Rev Anticancer Ther. 2016;16(11):1109–1118.
  • Ferrari SM, Bocci G, Di Desidero T, et al. Vandetanib has antineoplastic activity in anaplastic thyroid cancer, in vitro and in vivo. Oncol Rep. 2018;39(5):2306–2314.
  • Ferrari SM, Bocci G, Di Desidero T, et al. Lenvatinib exhibits antineoplastic activity in anaplastic thyroid cancer in vitro and in vivo. Oncol Rep. 2018;39(5):2225–2234.
  • Antonelli A, Ferrari SM, Fallahi P, et al. Thiazolidinediones and antiblastics in primary human anaplastic thyroid cancer cells. Clin Endocrinol (Oxf). 2009;70(6):946–953.
  • Antonelli A, Ferrari SM, Fallahi P, et al. Primary cell cultures from anaplastic thyroid cancer obtained by fine-needle aspiration used for chemosensitivity tests. Clin Endocrinol (Oxf). 2008;69(1):148–152.
  • Antonelli A, Ferrari SM, Fallahi P, et al. Evaluation of the sensitivity to chemotherapeutics or thiazolidinediones of primary anaplastic thyroid cancer cells obtained by fine-needle aspiration. Eur J Endocrinol. 2008;159(3):283–291.
  • Miccoli P, Materazzi G, Antonelli A, et al. New trends in the treatment of undifferentiated carcinomas of the thyroid. Langenbecks Arch Surg. 2007;392(4):397–404.
  • Liu JW, Chen C, Loh EW, et al. Tyrosine kinase inhibitors for advanced or metastatic thyroid cancer: a meta-analysis of randomized controlled trials. Curr Med Res Opin. 2018;34(5):795–803.
  • Samimi H, Fallah P, Naderi Sohi A, et al. Precision medicine approach to anaplastic thyroid cancer: advances in targeted drug therapy based on specific signaling pathways. Acta Med Iran. 2017;55(3):200–208.
  • Kebebew E, Greenspan FS, Clark OH, et al. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer. 2005;103(7):1330–1335.
  • Samimi H, Zaki Dizaji M, Ghadami M, et al. Essential genes in thyroid cancers: focus on fascin. J Diabetes Metab Disord. 2013;12(1):32.
  • Smith N, Nucera C. Personalized therapy in patients with anaplastic thyroid cancer: targeting genetic and epigenetic alterations. J Clin Endocrinol Metab. 2015;100(1):35–42.
  • Miccoli P, Antonelli A, Spinelli C, et al. Completion total thyroidectomy in children with thyroid cancer secondary to the Chernobyl accident. Arch Surg. 1998;133(1):89–93.
  • Ferrari SM, Ruffilli I, Centanni M, et al. Lenvatinib in the therapy of aggressive thyroid cancer: state of the art and new perspectives with patents recently applied. Recent Pat Anticancer Drug Discov. 2018;13(2):201–208.
  • Antonelli A, Miccoli P, Fallahi P, et al. Role of neck ultrasonography in the follow-up of children operated on for thyroid papillary cancer. Thyroid. 2003;13(5):479–484.
  • Akaishi J, Sugino K, Kitagawa W, et al. Prognostic factors and treatment outcomes of 100 cases of anaplastic thyroid carcinoma. Thyroid. 2011;21(11):1183–1189.
  • Are C, Shaha AR. Anaplastic thyroid carcinoma: biology, pathogenesis, prognostic factors, and treatment approaches. Ann Surg Oncol. 2006;13(4):453–464.
  • De Crevoisier R, Baudin E, Bachelot A, et al. Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy. Int J Radiat Oncol Biol Phys. 2004;60(4):1137–1143.
  • Pinto N, Black M, Patel K, et al. Genomically driven precision medicine to improve outcomes in anaplastic thyroid cancer. J Oncol. 2014;2014:936285.
  • Smallridge RC, Ain KB, Asa SL, et al. American thyroid association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 2012;22(11):1104–1139.
  • Antonelli A, Fallahi P, Ferrari SM, et al. New targeted therapies for thyroid cancer. Curr Genomics. 2011;12(8):626–631.
  • Smallridge RC, Marlow LA, Copland JA. Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. Endocr Relat Cancer. 2009;16(1):17–44.
  • Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005;12(2):245–262.
  • Perri F, Pezzullo L, Chiofalo MG, et al. Targeted therapy: a new hope for thyroid carcinomas. Crit Rev Oncol Hematol. 2015;94(1):55–63.
  • Duquette M, Sadow PM, Lawler J, et al. Thrombospondin-1 silencing down-regulates integrin expression levels in human anaplastic thyroid cancer cells with BRAF(V600E): new insights in the host tissue adaptation and homeostasis of tumor microenvironment. Front Endocrinol (Lausanne). 2013;4:189.
  • Nucera C, Lawler J, Parangi S. BRAF(V600E) and microenvironment in thyroid cancer: a functional link to drive cancer progression. Cancer Res. 2011;71(7):2417–2422.
  • Lee J, Hwang JA, Lee EK. Recent progress of genome study for anaplastic thyroid cancer. Genomics Inform. 2013;11(2):68–75.
  • Murugan AK, Xing M. Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene. Cancer Res. 2011;71(13):4403–4411.
  • Pylayeva-Gupta Y, Grabocka E, Bar-Sagi D. RAS oncogenes: weaving a tumorigenic web. Nat Rev Cancer. 11(11):761–774.
  • Nikiforov YE. Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Pathol. 2008;21(2):S37–S43. Suppl2.
  • Nikiforova MN, Nikiforov YE. Molecular genetics of thyroid cancer: implications for diagnosis, treatment and prognosis. Expert Rev Mol Diagn. 2008;8(1):83–95.
  • Ruggeri RM, Campennì A, Baldari S, et al. What is new on thyroid cancer biomarkers. Biomark Insights. 2008;3:237–252.
  • Penna GC, Vaisman F, Vaisman M, et al. Molecular markers involved in tumorigenesis of thyroid carcinoma: focus on aggressive histotypes. Cytogenet Genome Res. 2016;150(3–4):194–207.
  • Su X, Jiang X, Wang W, et al. Association of telomerase reverse transcriptase promoter mutations with clinicopathological features and prognosis of thyroid cancer: a meta-analysis. Onco Targets Ther. 2016;9:6965–6976.
  • Polakis P. Wnt signaling and cancer. Genes Dev. 2000;14(15):1837–1851.
  • Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013;13(3):184–199.
  • O’Neill JP, Shaha AR. Anaplastic thyroid cancer. Oral Oncol. 2013;49(7):702–706.
  • Anastas JN, Moon RT. WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer. 2013;13(1):11–26.
  • Herbst RS. Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys. 2004;59(Suppl 2):21–26.
  • Knauf JA. Does the epidermal growth factor receptor play a role in the progression of thyroid cancer? Thyroid. 2011;21(11):1171–1174.
  • Yeh MW, Rougier JP, Park JW, et al. Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A. Endocr Relat Cancer. 2006;13(4):1173–1183.
  • Liu Z, Hou P, Ji M, et al. 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.
  • Bond JA, Wyllie FS, Rowson J, et al. In vitro reconstruction of tumour initiation in a human epithelium. Oncogene. 1994;9(1):281–290.
  • Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004;25(4):581–611.
  • Bunone G, Vigneri P, Mariani L, et al. Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features. Am J Pathol. 1999;155(6):1967–1976.
  • Sato K. Vascular endothelial growth factors and thyroid disorders. Endocr J. 2001;48(6):635–646.
  • Lennard CM, 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(5):552–558.
  • Xing M. Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer. Thyroid. 2010;20(7):697–706.
  • Kelly LM, Barilab G, Liu P, et al. Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer. Proc Natl Acad Sci U S A. 2014;111(11):4233–4238.
  • Demeure MJ, Aziz M, Rosenberg R, et al. Whole-genome sequencing of an aggressive BRAF wild-type papillary thyroid cancer identified EML4-ALK translocation as a therapeutic target. World J Surg. 2014;38(6):1296–1305.
  • Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol. 2011;7(10):569–580.
  • Placzkowski KA, Reddi HV, Grebe SK, et al. The role of the PAX8/PPARgamma fusion oncogene in thyroid cancer. PPAR Res. 2008;2008:672829.
  • Kim J, Lee Y, Cho HJ, et al. NTRK1 fusion in glioblastoma multiforme. PLoS One. 2014;9(3):e91940.
  • Vaishnavi A, Capelletti M, Le AT, et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med. 2013;19(11):1469–1472.
  • Morrison JA, Pike LA, Sams SB, et al. Thioredoxin interacting protein (TXNIP) is a novel tumor suppressor in thyroid cancer. Mol Cancer. 2014;13:62.
  • Fagin JA, Matsuo K, Karmakar A, et al. High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest. 1993;91(1):179–184.
  • Quiros RM, Ding HG, Gattuso P, et al. Evidence that one subset of anaplastic thyroid carcinomas are derived from papillary carcinomas due to BRAF and p53 mutations. Cancer. 2005;103(11):2261–2268.
  • Liu D, Yang C, Bojdani E, et al. Identification of RASAL1 as a major tumor suppressor gene in thyroid cancer. J Natl Cancer Inst. 2013;105(21):1617–1627.
  • Mahlknecht U, Hoelzer D. Histone acetylation modifiers in the pathogenesis of malignant disease. Mol Med. 2000;6(8):623–644.
  • Marks P, Rifkind RA, Richon VM, et al. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer. 2001;1(3):194–202.
  • Lin SF, Lin JD, Chou TC, et al. Utility of a histone deacetylase inhibitor (PXD101) for thyroid cancer treatment. PLoS One. 2013;8(10):e77684.
  • Chien W, Koeffler HP. Molecular biology of thyroid cancer. Thyroid Cancer. 2012;30:35–43.
  • Marini F, Luzi E, Brandi ML. MicroRNA role in thyroid cancer development. J Thyroid Res. 2011;2011:407123.
  • Xiong Y, Zhang L, Kebebew E. MiR-20a is upregulated in anaplastic thyroid cancer and targets LIMK1. PLoS One. 2014;9(5):e96103.
  • Wang J, Zhang KY, Liu SM, et al. Tumor-associated circulatingMicroRNAs as biomarkers of cancer. Molecules. 2014;19(2):1912–1938.
  • Guo Z, Hardin H, Lloyd RV. Cancer stem-like cells and thyroid cancer. Endocr Relat Cancer. 2014;21(5):T285–300.
  • Gao YJ, Li B, Wu XY, et al. Thyroid tumorinitiating cells: increasing evidence and opportunities for anticancer therapy (Review). Oncol Rep. 2014;31(3):1035–1042.
  • Nagayama Y, Shimamura M, Mitsutake N. Cancer stem cells in the thyroid. Front Endocrinol (Lausanne). 2016;7:20.
  • Antonelli A, La Motta C. Novel therapeutic clues in thyroid carcinomas: the role of targeting cancer stem cells. Med Res Rev. 2017;37(6):1299–1317.
  • Heiden KB, Williamson AJ, Doscas ME, et al. The sonic hedgehog signaling pathway maintains the cancer stem cell self-renewal of anaplastic thyroid cancer by inducing snail expression. J Clin Endocrinol Metab. 2014;99(11):E2178–E2187.
  • Malaguarnera R, Frasca F, Garozzo A, et al. Insulin receptor isoforms and insulin-like growth factor receptor in human follicular cell precursors from papillary thyroid cancer and normal thyroid. J Clin Endocrinol Metab. 2011;96(3):766–774.
  • Tseng LM, Huang PI, Chen YR, et al. Targeting signal transducer and activator of transcription 3 pathway by cucurbitacin I diminishes self-renewing and radiochemoresistant abilities in thyroid cancer-derived CD133+ cells. J Pharmacol Exp Ther. 2012;341:410–423.
  • Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367(18):1694–1703.
  • Kurata K, Onoda N, Noda S, et al. Growth arrest by activated BRAF and MEK inhibition in human anaplastic thyroid cancer cells. Int J Oncol. 2016;49(6):2303–2308.
  • Maverakis E, Cornelius LA, Bowen GM, et al. Metastatic melanoma - a review of current and future treatment options. Acta Derm Venereol. 2015;95(5):516–524.
  • Lim AM, Taylor GR, Fellowes A, et al. BRAF Inhibition in BRAFV600E-positive anaplastic thyroid carcinoma. J Natl Compr Canc Netw. 2016;14(3):249–254.
  • Cabanillas ME, Busaidy NL, Khan SA, et al. Molecular diagnostics and anaplastic thyroid carcinoma: the time has come to harvest the high hanging fruit. Int J Endocr Oncol. 2016;3(3):221–233.
  • Subbiah V, Bang YJ, Lassen UN, et al. ROAR: a phase 2, open-label study in patients (pts) with BRAF V600E–mutated rare cancers to investigate the efficacy and safety of dabrafenib (D) and trametinib (T) combination therapy. J Clin Oncol. 2016. Abstract TPS2604.
  • [No authors listed]. Dabrafenib plus trametinib is active in BRAFV600E anaplastic thyroid cancer. Cancer Discov. 2018;8(1):9.
  • Subbiah V, Kreitman RJ, Wainberg ZA, et al. Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer. J Clin Oncol. 2018;36(1):7–13.
  • Cabanillas ME, Ferrarotto R, Garden AS, et al. Neoadjuvant BRAF- and immune-directed therapy for anaplastic thyroid carcinoma. Thyroid. 2018;28(7):945–951.
  • Kim KB, Cabanillas ME, Lazar AJ, et al. Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation. Thyroid. 2013;23(10):1277–1283.
  • Rosove MH, Peddi PF, Glaspy JA. BRAF V600E inhibition in anaplastic thyroid cancer. N Engl J Med. 2013;368(7):684–685.
  • Prager GW, Koperek O, Mayerhoefer ME, et al. Sustained response to vemurafenib in a BRAFV600E-Mutated anaplastic thyroid carcinoma patient. Thyroid. 2016;26(10):1515–1516.
  • Marten KA, Gudena VK. Use of vemurafenib in anaplastic thyroid carcinoma: a case report. Cancer Biol Ther. 2015;16(10):1430–1433.
  • Hyman DM, Puzanov I, Subbiah V, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015;373(8):726–736.
  • Croyle M, Akeno N, Knauf JA, et al. RET/PTC-induced 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(11):4183–4191.
  • Lopez JP, Wang-Rodriguez J, Chang CY, et al. Gefitinib (Iressa) potentiates the effect of ionizing radiation in thyroid cancer cell lines. Laryngoscope. 2008;118(8):1372–1376.
  • Nobuhara Y, Onoda N, Yamashita Y, et al. Efficacy of epidermal growth factor receptor-targeted molecular therapy in anaplastic thyroid cancer cell lines. Br J Cancer. 2005;92(6):1110–1116.
  • Fury MG, Solit DB, Su YB, et al. A phase I trial of intermittent high-dose gefitinib and fixed-dose docetaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2007;59(4):467–475.
  • Wells SA Jr, Gosnell JE, Gagel RF, et al. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol. 2010;28(5):767–772.
  • Thornton K, Kim G, Maher VE, et al. Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary. Clin Cancer Res. 2012;18(14):3722–3730.
  • Wunderlich A, Khoruzhyk M, Roth S, et al. Pretherapeutic drug evaluation by tumor xenografting in anaplastic thyroid cancer. J Surg Res. 2013;185(2):676–683.
  • Leboulleux S, Bastholt L, Krause T, et al. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol. 2012;13(9):897–905.
  • Sherman SI, Jarzab B, Cabanillas ME, et al. A phase II trial of the multitargeted kinase inhibitor E7080 in advanced radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). J Clin Oncol. 2011. Abstract 5503.
  • Tohyama O, Matsui J, Kodama K, et al. Antitumor activity of lenvatinib (e7080): an angiogenesis inhibitor that targets multiple receptor tyrosine kinases in preclinical human thyroid cancer models. J Thyroid Res. 2014;2014:638747.
  • Takahashi S, Kiyota N, Yamazaki T, et al. Phase II study of lenvatinib in patients with differentiated, medullary, and anaplastic thyroid cancer: final analysis results. J Clin Oncol. 2016. Abstract 6088.
  • Tahara M, Kiyota N, Yamazaki T, et al. Lenvatinib for anaplastic thyroid cancer. Front Oncol. 2017;7:25.
  • Kloos RT, Ringel MD, Knopp MV, et al. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol. 2009;27(10):1675–1684.
  • Gupta-Abramson V, Troxel AB, Nellore A, et al. Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol. 2008;26(29):4714–4719.
  • Hoftijzer H, Heemstra KA, Morreau H, et al. Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma. Eur J Endocrinol. 2009;161(6):923–931.
  • Brose MS, Nutting CM, Jarzab B, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014;384(9940):319–328.
  • Savvides P, Nagaiah G, Lavertu P, et al. Phase II trial of sorafenib in patients with advanced anaplastic carcinoma of the thyroid. Thyroid. 2013;23(5):600–604.
  • Ito Y, Onoda N, Ito KI, et al. Sorafenib in Japanese patients with locally advanced or metastatic medullary thyroid carcinoma and anaplastic thyroid carcinoma. Thyroid. 2017;27(9):1142–1148.
  • Chen G, Nicula D, Renko K, et al. Synergistic anti-proliferative effect of metformin and sorafenib on growth of anaplastic thyroid cancer cells and their stem cells. Oncol Rep. 2015;33(4):1994–2000.
  • Cohen EE, Rosen LS, Vokes EE, 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(29):4708–4713.
  • Cohen EE, Tortorici M, Kim S, et al. A phase II trial of axitinib in patients with various histologic subtypes of advanced thyroid cancer: long-term outcomes and pharmacokinetic/pharmacodynamic analyses. Cancer Chemother Pharmacol. 2014;74(6):1261–1270.
  • Kim DW, Jo YS, Jung HS, et al. An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases. J Clin Endocrinol Metab. 2006;91(10):4070–4076.
  • Carr LL, Mankoff DA, Goulart BH, 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(21):5260–5268.
  • Ravaud A, de la Fouchardière C, Caron P, et al. 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.
  • Grande E, Capdevila J, Díez JJ, et al. A significant response to sunitinib in a patient with anaplastic thyroid carcinoma. J Res Med Sci. 2013;18(7):623–625.
  • Cohen EE, Needles BM, Cullen KJ, et al. Phase 2 study of sunitinib in refractory thyroid cancer. J Clin Oncol. 2008. Abstract 6025.
  • Goulart B, Carr L, Martins RG, 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. Abstract 6062.
  • Antonelli A, Bocci G, La Motta C, et al. CLM94, a novel cyclic amide with anti-VEGFR-2 and antiangiogenic properties, is active against primary anaplastic thyroid cancer in vitro and in vivo. J Clin Endocrinol Metab. 2012;97(4):E528–E536.
  • Ferrari SM, Fallahi P, La Motta C, et al. Antineoplastic activity of the multitarget tyrosine kinase inhibitors CLM3 and CLM94 in medullary thyroid cancer in vitro. Surgery. 2014;156(5):1167–1176.
  • Antonelli A, Bocci G, Fallahi P, et al. CLM3, a multitarget tyrosine kinase inhibitor with antiangiogenic properties, is active against primary anaplastic thyroid cancer in vitro and in vivo. J Clin Endocrinol Metab. 2014;99(4):E572–E581.
  • Fallahi P, Ferrari SM, La Motta C, et al. CLM29 and CLM24, pyrazolopyrimidine derivatives, have antitumoral activity in vitro in anaplastic thyroid cancer, with or without BRAF mutation. Endocrine. 2016;53(1):136–144.
  • Kanthou C, Tozer GM. Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies. Int J Exp Pathol. 2009;90(3):284–294.
  • Dowlati A, Robertson K, Cooney M, et al. A phase I pharmacokinetic and translational study of the novel vascular targeting agent combretastatin a-4 phosphate on a single-dose intravenous schedule in patients with advanced cancer. Cancer Res. 2002;62(12):3408–3416.
  • Sosa JA, Balkissoon J, Lu SP, et al. Thyroidectomy followed by fosbretabulin (CA4P) combination regimen appears to suggest improvement in patient survival in anaplastic thyroid cancer. Surgery. 2012;152(6):1078–1087.
  • Sosa JA, Elisei R, Jarzab B, et al. Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma. Thyroid. 2014;24(2):232–240.
  • Onoda N, Sugino K, Higashiyama T, et al. The safety and efficacy of weekly paclitaxel administration for anaplastic thyroid cancer patients: a nationwide prospective study. Thyroid. 2016;26(9):1293–1299.
  • Keir ME, Butte MJ, Freeman GJ, et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.
  • Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–2465.
  • Ahn S, Kim TH, Kim SW, et al. Comprehensive screening for PD-L1 expression in thyroid cancer. Endocr Relat Cancer. 2017;24(2):97–106.
  • Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–2454.
  • Brauner E, Gunda V, Vanden Borre P, et al. Combining BRAF inhibitor and anti PD-L1 antibody dramatically improves tumor regression and anti tumor immunity in an immunocompetent murine model of anaplastic thyroid cancer. Oncotarget. 2016;7(13):17194–17211.
  • Iyer PC, Dadu R, Gule-Monroe M, et al. Salvage pembrolizumab added to kinase inhibitor therapy for the treatment of anaplastic thyroid carcinoma. J Immunother Cancer. 2018;6(1):68.
  • Hayashi N, Nakamori S, Hiraoka N, et al. Antitumor effects of peroxisome proliferator activate receptor gamma ligands on anaplastic thyroid carcinoma. Int J Oncol. 2004;24(1):89–95.
  • Marlow LA, Reynolds LA, Cleland AS, et al. Reactivation of suppressed RhoB is a critical step for the inhibition of anaplastic thyroid cancer growth. Cancer Res. 2009;69(4):1536–1544.
  • Aiello A, Pandini G, Frasca F, et al. Peroxisomal proliferator-activated receptor-gamma agonists induce partial reversion of epithelial-mesenchymal transition in anaplastic thyroid cancer cells. Endocrinology. 2006;147:4463–4475.
  • Antonelli A, Fallahi P, Ferrari SM, et al. Dedifferentiated thyroid cancer: a therapeutic challenge. Biomed Pharmacother. 2008;62(8):559–563.
  • Chung SH, Onoda N, Ishikawa T, et al. Peroxisome proliferator-activated receptor gamma activation induces cell cycle arrest via the p53-independent pathway in human anaplastic thyroid cancer cells. Jpn J Cancer Res. 2002;93(12):1358–1365.
  • Smallridge RC, Copland JA, Brose MS, et al. Efatutazone, an oral PPAR-γ agonist, in combination with paclitaxel in anaplastic thyroid cancer: results of a multicenter phase 1 trial. J Clin Endocrinol Metab. 2013;98(6):2392–2400.
  • Hombach-Klonisch S, Natarajan S, Thanasupawat T, et al. Mechanisms of therapeutic resistance in cancer (stem) cells with emphasis on thyroid cancer cells. Front Endocrinol (Lausanne). 2014;5:37.
  • Vicari L, Colarossi C, Giuffrida D, et al. Cancer stem cells as a potential therapeutic target in thyroid carcinoma. Oncol Lett. 2016;12(4):2254–2260.
  • Newell DR. Flasks, fibres and flanks–pre-clinical tumour models for predicting clinical antitumour activity. Br J Cancer. 2001;84(10):1289–1290.
  • Schroyens W, Tueni E, Dodion P, et al. Validation of clinical predictive value of in vitro colorimetric chemosensitivity assay in head and neck cancer. Eur J Cancer. 1990;26(7):834–838.
  • Blumenthal RD, Goldenberg DM. Methods and goals for the use of in vitro and in vivo chemosensitivity testing. Mol Biotechnol. 2007;35(2):185–197.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.