The role of molecular testing in thyroid tumors
https://doi.org/10.14341/probl12491
Abstract
¹I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; ²Endocrinology Research Centre, Moscow, Russia
Thyroid cancer is the most common endocrine gland cancer. In the last few decades, the molecular diagnostics for thyroid tumors have been widely researched. It is one of the few cancers whose incidence has increased in recent years from microcarcinomas to common, large forms, in all age groups, from children to the elder people. Most researches focus on the genetic basis, since our current knowledge of the genetic background of various forms of thyroid cancer is far from being complete. Molecular and genetic research has several main directions: firstly, differential diagnosis of thyroid tumors, secondly, the prognostic value of detected mutations in thyroid cancer, and thirdly, targeted therapy for aggressive or radioactive iodine-resistant forms of thyroid cancer. In this review, we wanted to update our understanding and describe the prevailing advances in molecular genetics of thyroid cancer, focusing on the main genes associated with the pathology and their potential application in clinical practice.
About the Authors
Vera A. Kachko
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
postgraduate student
Nadezhda M. Platonova
Endocrinology Research Centre,
Russian Federation
Russian Federation
MD, PhD
Vladimir E. Vanushko
Endocrinology Research Centre
Russian Federation
Russian Federation
MD, PhD
Boris M. Shifman
Endocrinology Research Centre
Russian Federation
Russian Federation
MD, PhD student
References
1. Brito JP, Yarur AJ, Prokop LJ, et al. Prevalence of thyroid cancer in multinodular goiter vs. single nodule: a systematic review and meta-analysis. Thyroid. 2013;23(4):449−455. doi: 10.1089/thy.2012.0156.
2. Kitahara CM, Sosa JA. The changing incidence of thyroid cancer. Nat Rev Endocrinol. 2016;12(11):646−653. doi: 10.1038/nrendo.2016.110.
3. Бельцевич Д.Г., Ванушко В.Э., Румянцев П.О., и др. Российские клинические рекомендации по диагностике и лечению высокодифференцированного рака щитовидной железы у взрослых, 2017 год // Эндокринная хирургия. — 2017. — Т. 11. — №1. — С. 6–27. [Beltsevich DG, Vanushko VE, Rumyantsev PO, et al. 2017 Russian clinical practice guidelines for differentiated thyroid cancer diagnosis and treatment. Endocrine Surgery. 2017;11(1):6−27. (In Russ.)] doi: 10.14341/serg201716-27.
4. Cibas ES, Ali SZ. The 2017 Bethesda system for reporting thyroid cytopathology. Thyroid. 2017;27(11):1341−1346. doi: 10.1089/thy.2017.0500.
5. Hsiao SJ, Nikiforov Y. Molecular approaches to thyroid cancer diagnosis. Endocr Relat Cancer. 2014;21(5):T301−313. doi: 10.1530/ERC-14-0166.
6. Oczko-Wojciechowska M, Kotecka-Blicharz A, Krajewska J, et al. European perspective on the use of molecular tests in the diagnosis and therapy of thyroid neoplasms. Gland Surg. 2020;9(2):S69−S76. doi: 10.21037/gs.2019.10.26.
7. Goodarzi E, Moslem A, Feizhadad H, et al. Epidemiology, incidence and mortality of thyroid cancer and their relationship with the human development index in the world: an ecology study in 2018. Adv Hum Biol. 2019;9(2):162–167.
8. ASCO. [Internet] Thyroid Cancer: Statistics. [cited 2020 April 22]. Available from: https://www.cancer.net/cancer-types/thyroid-cancer/statistics.
9. Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016;388(10061):2783–2795. doi: 10.1016/S0140-6736(16)30172-6.
10. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013;13(3):184−199. doi: 10.1038/nrc3431.
11. Guilmette J, Nose V. Hereditary and familial thyroid tumours. Histopathology. 2018;72(1):70−81. doi: 10.1111/his.13373.
12. Yang PS, Ngeow J. Familial non-medullary thyroid cancer: Unraveling the genetic maze. Endocr Relat Cancer. 2016;23(12):R577−R595. doi: 10.1530/ERC-16-0067.
13. Ruiz-Ferrer M, Fernandez RM, Navarro E, et al. G534E Variant in HABP2 and Nonmedullary Thyroid Cancer. Thyroid. 2016;26(7):987−988. doi: 10.1089/thy.2016.0193.
14. Ye F, Gao H, Xiao L, et al. Whole exome and target sequencing identifies MAP2K5 as novel susceptibility gene for familial non-medullary thyroid carcinoma. Int J Cancer. 2019;144(6):1321−1330. doi: 10.1002/ijc.31825.
15. Luzón-Toro B, Fernández RM, Villalba-Benito L, et al. Influencers on thyroid cancer onset: molecular genetic basis. Genes (Basel). 2019;10(11):913. doi: 10.3390/genes10110913.
16. Tirrò E, Martorana F, Romano C, et al. Molecular alterations in thyroid cancer: from bench to clinical practice. Genes (Basel). 2019;10(9):709. doi: 10.3390/genes10090709.
17. Vella V, Malaguarnera R. The emerging role of insulin receptor isoforms in thyroid cancer: clinical implications and new perspectives. Int. J. Mol. Sci. 2018;19(12):3814. doi: 10.3390/ijms19123814.
18. Zarkesh M, Zadeh-Vakili A, Azizi F, et al. Altered epigenetic mechanisms in thyroid cancer subtypes. Mol Diagn Ther. 2018;22(1):41−56. doi: 10.1007/s40291-017-0303-y.
19. Romei C, Ciampi R, Elisei R. A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma. Nat Rev Endocrinol. 2016;12(4):192−202. doi: 10.1038/nrendo.2016.11.
20. Khan MS, Qadri Q, Makhdoomi MJ, et al. RET/PTC gene rearrangements in thyroid carcinogenesis: assessment and clinico-pathological correlations. Pathol Oncol Res. 2018;26(1):507−513. doi: 10.1007/s12253-018-0540-3.
21. Mulligan LM. RET revisited: Expanding the oncogenic portfolio. Nat Rev Cancer. 2014;14(3):173−186. doi: 10.1038/nrc3680.
22. Wells SA. Advances in the management of MEN2: From improved surgical and medical treatment to novel kinase inhibitors. Endocr Relat Cancer. 2018;25(2):T1−T13. doi: 10.1530/ERC-17-0325.
23. Kunstman JW, Juhlin CC, Goh G, et al. Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet. 2015;24(8):2318−2329. doi: 10.1093/hmg/ddu749.
24. Agrawal N, Akbani R, Aksoy BA, et al. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676−690. doi: 10.1016/j.cell.2014.09.050.
25. Santarpia L, Myers JN, Sherman SI, et al. Genetic alterations in the RAS/RAF/mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signaling pathway in the follicular variant of papillary thyroid carcinoma. Cancer. 2010;116(12):2974−2983. doi: 10.1002/cncr.25061.
26. Milella M, Falcone I, Conciatori F, et al. PTEN: Multiple functions in human malignant tumors. Front Oncol. 2015;5:24. doi: 10.3389/fonc.2015.00024.
27. Lozada JR, Basili T, Pareja F, et al. Solid papillary breast carcinomas resembling the tall cell variant of papillary thyroid neoplasms (solid papillary carcinomas with reverse polarity) harbour recurrent mutations affecting IDH2 and PIK3CA: A validation cohort. Histopathology. 2018;73(2):339−344. doi: 10.1111/his.13522.
28. Nishino M, Nikiforova M. Update on molecular testing for cytologically indeterminate thyroid nodules. Arch Pathol Lab Med. 2018;142(4):446−457. doi: 10.5858/arpa.2017-0174-RA.
29. Orlo MS, He X, Peterson C, et al. Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes. Am J Hum Genet. 2013;92(1):76−80. doi: 10.1016/j.ajhg.2012.10.021.
30. Landa I, Ibrahimpasic T, Boucai L, et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest. 2016;126(3):1052−1066. doi: 10.1172/JCI85271.
31. Marques IJ, Moura MM, Cabrera R, et al. Identification of somatic TERT promoter mutations in familial nonmedullary thyroid carcinomas. Clin Endocrinol. 2017;87(4):394−399. doi: 10.1111/cen.13375.
32. Bonhomme B, Godbert Y, Perot G, et al. Molecular pathology of anaplastic thyroid carcinomas: a retrospective study of 144 cases. Thyroid. 2017;27(5):682−692. doi: 10.1089/thy.2016.0254.
33. Gerber TS, Schad A, Hartmann N, et al. Targeted next-generation sequencing of cancer genes in poorly di erentiated thyroid cancer. Endocr Connect. 2018;7(1):47−55. doi: 10.1530/EC-17-0290.
34. Guha T, Malkin D. Inherited TP53 mutations and the li-fraumeni syndrome. Cold Spring Harb Perspect Med. 2017;7(4):a026187. doi: 10.1101/cshperspect.a026187.
35. Sponziello M, Benvenuti S, Gentile A, et al. Whole exome sequencing identifies a germline MET mutation in two siblings with hereditary wild-type RET medullary thyroid cancer. Hum Mutat. 2018;39(3):371−377. doi: 10.1002/humu.23378.
36. Bae JS, Kim Y, Jeon S, et al. Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation. Diagn Pathol. 2016;11:21. doi: 10.1186/s13000-016-0458-6.
37. Borowczyk M, Szczepanek-Parulska E, Debicki S, et al. Differences in mutational profile between follicular thyroid carcinoma and follicular thyroid adenoma identified using next generation sequencing. Int J Mol Sci. 2019;20(13):3126. doi: 10.3390/ijms20133126.
38. Hincza K, Kowalik A, Kowalska A. Current knowledge of germline genetic risk factors for the development of non-medullary thyroid cancer. Genes. 2019;10(7):482. doi: 10.3390/genes10070482.
39. Lam AK, Saremi N. Cribriform-morular variant of papillary thyroid carcinoma: A distinctive type of thyroid cancer. Endocr Relat Cancer. 2017;24(4):R109–R121. doi: 10.1530/ERC-17-0014.
40. Turan S, Bastepe M. GNAS spectrum of disorders. Curr Osteoporos Rep. 2015;13(3):146−158. doi: 10.1007/s11914-015-0268-x.
41. Davies TF, Yin X, Latif R. The genetics of the thyroid stimulating hormone receptor: history and relevance. Thyroid. 2010;20(7):727–736. doi: 10.1089/thy.2010.1638.
42. Karunamurthy A, Panebianco F, J Hsiao S, et al. Prevalence and phenotypic correlations of EIF1AX mutations in thyroid nodules. Endocr Relat Cancer. 2016;23(4):295−301. doi: 10.1530/erc-16-0043.
43. Leeman-Neill RJ, Kelly LM, Liu P, et al. ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer. Cancer. 2014;120(6):799–807. doi: 10.1002/cncr.28484.
44. Younis E. Oncogenesis of thyroid cancer. Asian Pac J Cancer Prev. 2017;18(5):1191−1199. doi: 10.22034/APJCP.2017.18.5.1191.
45. Zhang Y, Yu J, Grachtchouk V, et al. Genomic binding of PAX8-PPARG fusion protein regulates cancer-related pathways and alters the immune landscape of thyroid cancer. Oncotarget 2017;8(4):5761−5773. doi: 10.18632/oncotarget.14050.
46. Liu T, Yuan X, Xu D. Cancer-Specific telomerase reverse transcriptase (TERT) promoter mutations: biological and clinical implications. Genes. 2016;7(7):38. doi: 10.3390/genes7070038.
47. Jin A, Xu J, Wang Y. The role of TERT promoter mutations in postoperative and preoperative diagnosis and prognosis in thyroid cancer. Medicine (Baltimore). 2018;97(29):e11548. doi: 10.1097/MD.0000000000011548.
48. Kelly LM, Barila 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 USA. 2014;111(11):4233−4238. doi: 10.1073/pnas.1321937111.
49. Bastos AU, de Jesus AC, Cerutti JM. ETV6-NTRK3 and STRN-ALK kinase fusions are recurrent events in papillary thyroid cancer of adult population. Eur J Endocrinol. 2018;178(1):83−91. doi: 10.1530/EJE-17-0499.
50. Cao Z, Gao Q, Fu M, et al. Anaplastic lymphoma kinase fusions: Roles in cancer and therapeutic perspectives. Oncol Lett. 2019;17(2):2020−2030. doi: 10.3892/ol.2018.9856.
51. Molinaro E, Romei C, Biagini A, et al. Anaplastic thyroid carcinoma: From clinicopathology to genetics and advanced therapies. Nat Rev Endocrinol. 2017;13(11):644−660. doi: 10.1038/nrendo.2017.76.
52. Manzella L, Stella S, Pennisi MS, et al. New Insights in Thyroid Cancer and p53 Family Proteins. Int J Mol Sci. 2017;18(6):1325. doi: 10.3390/ijms18061325.
53. Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676−690. doi: 10.1016/j.cell.2014.09.050.
54. Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinology. 2011;7(10):569−580. doi: 10.1038/nrendo.2011.142.
55. Muzza M, Colombo C, Rossi S, et al. Telomerase in differentiated thyroid cancer: promoter mutations, expression and localization. Mol Cell Endocrinol. 2015;399:288−295. doi: 10.1016/j.mce.2014.10.019.
56. Rusinek D, Pfeifer A, Krajewska J, et al. Coexistence of TERT promoter mutations and the BRAF V600E alteration and its impact on histopathological features of papillary thyroid carcinoma in a selected series of polish patients. Int J Mol Sci. 2018;19(9):2647. doi: 10.3390/ijms19092647.
57. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1−133. doi: 10.1089/thy.2015.0020.
58. Gharib H, Papini E, Garber J, et al. American Association of Clinical Endocrinologists, American College of Endo-crinology, and Associazione Medici Endocrinologi Medical guidelines for clinical practice for the diagnosis and management of thyroid nodules—2016 update. Endocr Pract. 2016;22(5):622–639. doi: 10.4158/EP161208.
59. Chudova D, Wilde JI, Wang ET, et al. Molecular classification of thyroid nodules using high-dimensionality genomic data. J Clin Endocrinol Metab. 2010;95(12):5296−304. doi: 10.1210/jc.2010-1087.
60. Alexander EK, Kennedy GC, Baloch ZW, et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012;367(8):705−715. doi: 10.1056/NEJMoa1203208.
61. Patel KN, Angell TE, Babiarz J, et al. Performance of a genomic sequencing classifier for the preoperative diagnosis of cytologically indeterminate thyroid nodules. JAMA Surg. 2018;153(9):817−824. doi: 10.1001/jamasurg.2018.1153.
62. Nikiforov YE, Carty SE, Chiosea SI, et al. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer. 2014;120(23):3627−3634. doi: 10.1002/cncr.29038.
63. Steward DL, Carty SE, Sippel RS, et al. Performance of a multigene genomic classifier in thyroid nodules with indeterminate cytology. JAMA Oncol. 2019;5(2):204−212. doi: 10.1001/jamaoncol.2018.4616.
64. Lithwick-Yanai G, Dromi N, Shtabsky A, et al. Multicentre validation of a microRNA-based assay for diagnosing indeterminate thyroid nodules utilising fine needle aspirate smears. J Clin Pathol. 2017;70(6):500−507. doi: 10.1136/jclinpath-2016-204089.
65. Labourier E, Shifrin A, Busseniers AE, et al. Molecular testing for miRNA, mRNA, and DNA on fine-needle aspiration improves the preoperative diagnosis of thyroid nodules with indeterminate cytology. J Clin Endocrinol Metab. 2015;100(7):2743−2750. doi: 10.1210/jc.2015-1158.
66. Naoum GE, Morkos M, Kim B, Arafat W. Novel targeted therapies and immunotherapy for advanced thyroid cancers. Mol Cancer. 2018;17(1):51. doi: 10.1186/s12943-018-0786-0.
67. Tufano RP, Teixeira GV, Bishop J, et al. BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment: a systematic review and meta-analysis. Medicine (Baltimore). 2012;91(5):274–286. doi: 10.1097/MD.0b013e31826a9c71.
68. Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. Jama. 2013;309(14):1493–1501. doi: 10.1001/jama.2013.3190.
69. Massimino M, Tirro E, Stella S, et al. Effect of combined epigenetic treatments and ectopic NIS expression on undifferentiated thyroid cancer cells. Anticancer Res. 2018;38(12):6653−6662. doi: 10.21873/anticanres.13032.
70. Massimino M, Vigneri P, Fallica M, et al. IRF5 promotes the proliferation of human thyroid cancer cells. Mol Cancer. 2012;11:21. doi: 10.1186/1476-4598-11-21.
71. Priya SR, Dravid CS, Digumarti R, et al. Targeted therapy for medullary thyroid cancer: a review. Front Oncol. 2017;7:238. doi: 10.3389/fonc.2017.00238.
72. Faugeras L, Pirson AS, Donckier J, et al. Refractory thyroid carcinoma: Which systemic treatment to use? Ther Adv Med Oncol. 2018;10:1758834017752853. doi: 10.1177/1758834017752853.
73. Tumino D, Frasca F, Newbold K. Updates on the management of advanced, metastatic, and radioiodine refractory differentiated thyroid cancer. Front Endocrinol (Lausanne). 2017;8:312. doi: 10.3389/fendo.2017.00312.
74. Acquaviva G, Visani M, Repaci A, et al. Molecular pathology of thyroid tumours of follicular cells: A review of genetic alterations and their clinicopathological relevance. Histopathology. 2018;72(1):6−31. doi: 10.1111/his.13380.
75. Bikas A, Vachhani Sh, Jensen K, et al. Targeted therapies in thyroid cancer: an extensive review of the literature. Expert Rev Clin Pharmacol. 2016;9(10):1299−1313. doi: 10.1080/17512433.2016.1204230.
76. Krajewska J, Gawlik T, Jarzab B. Advances in small molecule therapy for treating metastatic thyroid cancer. Expert Opin Pharmacother. 2017;18(11):1049−1060. doi: 10.1080/14656566.2017.1340939.
77. Rao SN, Zafereo M, Dadu R, et al. Patterns of treatment failure in anaplastic thyroid carcinoma. Thyroid. 2017;27(5):672–681. doi: 10.1089/thy.2016.0395.
78. Sun Y, Du F, Gao M, et al. Anlotinib for the treatment of patients with locally advanced or metastatic medullary thyroid cancer. Thyroid. 2018;28(11):1455−1461. doi: 10.1089/thy.2018.0022.
79. Li D, Tang PZ, Chen X, et al. Anlotinib treatment in locally advanced or metastatic medullary thyroid carcinoma: A multicenter, randomized, double-blind, placebo-controlled phase IIB trial. J Clin Oncol. 2019;37(15_Suppl):6019. doi: 10.1200/jco.2019.37.15_suppl.6019.
80. Locati LD, Licitra L, Agate L, et al. Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments. Cancer. 2014;120(17):2694−2703. doi: 10.1002/cncr.28766.
81. Lim SM, Chung WY, Nam KH, et al. An open label, multicenter, phase II study of dovitinib in advanced thyroid cancer. Eur J Cancer. 2015;51(12):1588‐1595. doi: 10.1016/j.ejca.2015.05.020.
82. Traynor K. Cabozantinib approved for advanced medullary thyroid cancer. Am J Health Syst Pharm. 2013;70(2):88. doi: 10.2146/news130005.
83. Schlumberger M, Elisei R, Muller S, et al. Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma. Ann Oncol. 2017;28(11):2813−2819. doi: 10.1093/annonc/mdx479.
84. Cabanillas ME, de Souza JA, Geyer S, et al. 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. doi: 10.1200/JCO.2017.73.0226.
85. Ha HT, Lee JS, Urba S, et al. A phase II study of imatinib in patients with advanced anaplastic thyroid cancer. Thyroid. 2010;20(9):975−980. doi: 10.1089/thy.2010.0057.
86. Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015;372(7):621–630. doi: 10.1056/NEJMoa1406470.
87. Cabanillas ME, Schlumberger M, Jarzab B, et al. A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: A clinical outcomes and biomarker assessment. Cancer. 2015;121(16):2749−2756. doi: 10.1002/cncr.29395.
88. Haddad RI, Nasr C, Bischoff L, et al. NCCN Guidelines Insights: thyroid carcinoma, version 2.2018. J Natl Compr Cancer Netw. 2018;16(12):1429−1440. doi: 10.6004/jnccn.2018.0089.
89. Bible KC, Suman VJ, Molina JR, et al. Effcacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: Results of a phase 2 consortium study. Lancet Oncol. 2010;11(10):962−972. doi: 10.1016/S1470-2045(10)70203-5.
90. Bible KC, Suman VJ, Molina JR, et al. A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H. J Clin Endocrinol Metab. 2014;99(5):1687−1693. doi: 10.1210/jc.2013-3713.
91. Bible KC, Suman VJ, Menefee ME, et al. A multiinstitutional phase 2 trial of pazopanib monotherapy in advanced anaplastic thyroid cancer. J Clin Endocrinol Metab. 2012;97(9):3179−3184. doi: 10.1210/jc.2012-1520.
92. Schneider TC, Abdulrahman RM, Corssmit EP, et al. Long-term analysis of the efficacy and tolerability of sorafenib in advanced radio-iodine refractory differentiated thyroid carcinoma: Final results of a phase II trial. Eur J Endocrinol. 2012;167(5):643−650. doi: 10.1530/EJE-12-0405.
93. Brose MS, Nutting CM, Jarzab B, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: Arandomised, double-blind, phase 3 trial. Lancet. 2014;384(9940):319−328. doi: 10.1016/S0140-6736(14)60421-9.
94. Bikas A, Kundra P, Desale S, et al. Phase 2 clinical trial of sunitinib as adjunctive treatment in patients with advanced differentiated thyroid cancer. Eur J Endocrinol. 2016;174(3):373−380. doi: 10.1530/EJE-15-0930.
95. 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. doi: 10.1158/1078-0432.CCR-10-0994.
96. Ravaud A, de la Fouchardiere 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. doi: 10.1016/j.ejca.2017.01.029.
97. 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. doi: 10.1016/S1470-2045(12)70335-2.
98. Wells SA, Jr. Robinson BG, Gagel RF, et al. 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. doi: 10.1200/JCO.2011.35.5040.
99. Thornton K, Kim G, Maher VE, et al. Vandetanib for the treatment of symptomatic or progressivemedullary 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. doi: 10.1158/1078-0432.ccr-12-0411.
100. Lin Y, Wang C, Gao W, et al. Overwhelming rapid metabolic and structural response to apatinib in radioiodine refractory differentiated thyroid cancer. Oncotarget. 2017;8(26):42252−42261. doi: 10.18632/oncotarget.15036.
101. Zhang X, Wang C, Lin Y. Pilot dose comparison of apatinib in chinese patients with progressive radioiodine-refractory di_erentiated thyroid cancer. J Clin Endocrinol Metab. 2018;103(10):3640−3646. doi: 10.1210/jc.2018-00381.
102. Falchook GS, Millward M, Hong D, et al. BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer. Thyroid. 2015;25(1):71–77. doi: 10.1089/thy.2014.0123.
103. Shah MH, Wirth L, Wirth LJ, et al. Results of randomized phase II trial of dabrafenib versus dabrafenib plus trametinib in BRAF-mutated papillary thyroid carcinoma. J Clin Oncol. 2017;35(15 suppl):6022. doi: 10.1200/JCO.2017.35.15_suppl.6022.
104. 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. doi: 10.1200/JCO.2017.73.6785.
105. Falchook GS, Millward M, Hong D, et al. BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer. Thyroid. 2015;25(1):71‐77. doi: 10.1089/thy.2014.0123.
106. Ho AL, Grewal RK, Leboeuf R, et al. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med. 2013;368(7):623−632. doi: 10.1056/NEJMoa1209288.
107. Brose MS, Cabanillas ME, Cohen EE, et al. 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. doi: 10.1016/S1470-2045(16)30166-8.
108. Doebele RC, Pilling AB, Aisner DL, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012;18(5):1472−1482. doi: 10.1158/1078-0432.CCR-11-2906.
109. Guan J, Wolfstetter G, Siaw J, et al. Anaplastic lymphoma kinase L1198F and G1201E mutations identified in anaplastic thyroid cancer patients are not ligand-independent. Oncotarget. 2017;8(7):11566−11578. doi: 10.18632/oncotarget.14141.
110. Godbert Y, Henriques de Figueiredo B, Bonichon F, et al. Remarkable response to crizotinib in woman with anaplastic lymphoma kinase-rearranged anaplastic thyroid carcinoma. J Clin Oncol. 2015;33(20):e84‐e87. doi: 10.1200/JCO.2013.49.6596.
111. Gambacorti-Passerini C, Orlov S, Zhang L, et al. Long-term e_ects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study. Am J Hematol. 2018;93(5):607−614. doi: 10.1002/ajh.25043.
112. Rolfo C, Ruiz R, Giovannetti E, et al. Entrectinib: A potent new TRK, ROS1, and ALK inhibitor. Expert Opin Investig Drugs. 2015;24(11):1493−1500. doi: 10.1517/13543784.2015.1096344.
113. Khotskaya YB, Holla VR, Farago AF, et al. Targeting TRK family proteins in cancer. Pharmacol Ther. 2017;173:58−66. doi: 10.1016/j.pharmthera.2017.02.006.
114. Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat. Rev Clin Oncol. 2018;15(12):731−747. doi: 10.1038/s41571-018-0113-0.
115. Drilon A, Nagasubramanian R, Blake JF, et al. A next-generation TRK kinase inhibitor overcomes acquired resistance to prior TRK kinase inhibition in patients with TRK fusion-positive solid tumors. Cancer Discov. 2017;7(9):963−972. doi: 10.1158/2159-8290.CD-17-0507.
116. Hong DS, Bauer TM, Lee JJ, et al. Larotrectinib in adult patients with solid tumours: A multi-centre, open-label, phase I dose-escalation study. Ann Oncol. 2019;30(2):325−331. doi: 10.1093/annonc/mdy539.
117. Borson-Chazot F, Dantony E, Illouz F, et al. Effect of buparlisib, a pan-class i pi3k inhibitor, in refractory follicular and poorly differentiated thyroid cancer. Thyroid. 2018;28(9):1174−1179. doi: 10.1089/thy.2017.0663.
118. Schneider TC, de Wit D, Links TP, et al. Beneficial effects of the mTOR inhibitor everolimus in patients with advanced medullary thyroid carcinoma: subgroup results of a phase II trial. Int J Endocrinol. 2015;2015:348124. doi: 10.1155/2015/348124.
119. Schneider TC, de Wit D, Links TP, et al. Everolimus in patientswith advanced follicular-derived thyroid cancer: results of a phase II clinical trial. J Clin Endocrinol. Metab. 2017;102(2):698−707. doi: 10.1210/jc.2016-2525.
120. Hanna GJ, Busaidy NL, Chau NG, et al. Genomic correlates of response to everolimus in aggressive radioiodine-refractory thyroid cancer: a phase II study. Clin Cancer Res. 2018;24(7):1546−1553. doi: 10.1158/1078-0432.CCR-17-2297.
121. Owonikoko TK, Zhang G, Lallani SB, et al. Evaluation of preclinical effcacy of everolimus and pasireotide in thyroid cancer cell lines and xenograft models. PLoS One. 2019;14(2):e0206309. doi: 10.1371/journal.pone.0206309.
122. Faggiano A, Modica R, Severino R, et al. The antiproliferative effect of pasireotide LAR alone and in combination with everolimus in patients with medullary thyroid cancer: A single-center, open-label, phase II, proof-of-concept study. Endocrine. 2018;62(1):46−56. doi: 10.1007/s12020-018-1583-7.
123. Sherman EJ, Dunn LA, Ho AL, et al. Phase 2 study evaluating the combination of sorafenib and temsirolimus in the treatment of radioactive iodine-refractory thyroid cancer. Cancer. 2017;123(21):4114–4121. doi: 10.1002/cncr.30861.
124. Manohar PM, Beesley LJ, Taylor JM, et al. Retrospective study of sirolimus and cyclophosphamide in patients with advanced differentiated thyroid cancers. J Thyroid Disord Ther. 2015;4(3):188. doi: 10.4172/2167-7948.1000188.
125. Smallridge RC, Copland JA, Brose MS, et al. Efatutazone, an oral PPAR-gamma 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. doi: 10.1210/jc.2013-1106.
126. Brose MS, Bible KC, Chow LQ, et al. Management of treatment-related toxicities in advanced medullary thyroid cancer. Cancer Treat Rev. 2018;66:64–73. doi: 10.1016/j.ctrv.2018.04.007.
127. Costa R, Carneiro BA, Chandra S, et al. Spotlight on lenvatinib in the treatment of thyroid cancer: Patient selection and perspectives. Drug Des Dev Ther. 2016;10:873−884. doi: 10.2147/DDDT.S93459.
128. Lopez JS, Banerji U. Combine and conquer: Challenges for targeted therapy combinations in early phase trials. Nat Rev Clin Oncol. 2017;14(1):57−66. doi: 10.1038/nrclinonc.2016.96.
129. Massimino M, Stella S, Tirro E, et al. Non ABL-directed inhibitors as alternative treatment strategies for chronic myeloid leukemia. Mol Cancer. 2018;17(1):56. doi: 10.1186/s12943-018-0805-1.
130. Pirosa MC, Leotta S, Cupri A, et al. Long-Term molecular remission achieved by antibody Anti-CD22 and ponatinib in a patient affected by Ph’+ Acute lymphoblastic leukemia relapsed after second allogeneic hematopoietic stem cell transplantation: a case report. Chemotherapy. 2018; 63(4):220−224. doi: 10.1159/000492941.
131. Tirro E, Massimino M, Romano C, et al. Chk1 inhibition restores inotuzumab ozogamicin citotoxicity in CD22-Positive cells expressing Mutant p53. Front Oncol. 2019;9:57. doi: 10.3389/fonc.2019.00057.
Supplementary files
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1. Figure 1. Key molecular signaling pathways involved in the development of thyroid cancer PI3K-mTOR, MAPK. | |
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2. Figure 2. Major genetic changes involved in carcinogenesis in various histological types of thyroid cancer. | |
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3. Table 1. The most significant genetic changes in tumors of the thyroid gland. | |
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| Type | author.submit.suppFile.tableResults | |
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4. Table 2. Frequency of occurrence of major genetic changes in various histological types of thyroid tumors | |
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| Type | author.submit.suppFile.tableResults | |
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5. Table 3. Main commercially available molecular genetic panels and their characteristics. | |
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6. Table 4. Targeted drugs for the treatment of aggressive forms of thyroid cancer. | |
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| Type | author.submit.suppFile.tableResults | |
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(32KB)
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For citations:
Kachko V.A., Platonova N.M., Vanushko V.E., Shifman B.M. The role of molecular testing in thyroid tumors. Problems of Endocrinology. 2020;66(3):33-46. https://doi.org/10.14341/probl12491
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