Indian Journal of Endocrine Surgery and Research

Register      Login

VOLUME 19 , ISSUE 1 ( January-June, 2024 ) > List of Articles


Targeted Therapy in Thyroid Cancer

Upander Kumar, Nancy Raja, Rambhit C Dwivedi, Ashwinee Rahalkar, Mithun Raam, Kul R Singh, Pooja Ramakant, Anand Mishra

Keywords : Advanced thyroid cancer, Personalized medicine, Radioiodine refractory thyroid cancer, Redifferentiating agents, Tyrosine kinase inhibitors

Citation Information : Kumar U, Raja N, Dwivedi RC, Rahalkar A, Raam M, Singh KR, Ramakant P, Mishra A. Targeted Therapy in Thyroid Cancer. 2024; 19 (1):30-46.

DOI: 10.5005/jp-journals-10088-11236

License: CC BY-NC 4.0

Published Online: 17-06-2024

Copyright Statement:  Copyright © 2024; The Author(s).


Personalized medicine for thyroid cancer (TC) involves tailoring treatment plans based on a patient's specific genetic makeup and tumor characteristics. This effective treatment strategy is ultimately improving patient outcomes and quality of life. Various tyrosine kinase inhibitors, serine/threonine kinase or B-Raf proto-oncogene (BRAF) and mitogen-activated protein kinase (MAPK/MEK) inhibitors, neurotrophic tyrosine receptor kinase (NTRK) fusion inhibitors, rearranged during transfection (RET) inhibitors, vascular endothelial growth factor (VEGFR) inhibitors, redifferentiating agents, and immunotherapies have shown promising results in the last decade since their introduction for treating thyroid cancer (ThyCa). These agents may be used for radioiodine refractory (RAIR) differentiated TC (DTC), disseminated, recurrent, residual anaplastic TC (ATC), and medullary TC (MTC). They hardly have any contraindications. The knowledge of their safety profile has expanded with more and more use. They have tolerable side effects and occasionally may require treatment discontinuation or switching to other agents. The armamentarium of available drugs and new targets is rapidly increasing with the results of clinical trials. Their use in pregnancy, the risk of hematological malignancy, geographical variations in their availability and cost, definitive guidelines, and managing drug resistance are current challenges. Advances in molecular diagnosis, artificial intelligence, and molecular scissors may completely revolutionize targeted therapy in the future.

PDF Share
  1. Agosto Salgado S, Kaye ER, Sargi Z, et al. Management of Advanced Thyroid Cancer: Overview, Advances, and Opportunities. Am Soc Clin Oncol Educ Book 2023;43:e389708. DOI: 10.1200/EDBK_389708.
  2. Lorusso L, Cappagli V, Valerio L, et al. Thyroid cancers: From surgery to current and future systemic therapies through their molecular identities. Int J Mol Sci MDPI AG 2021;22:1–24.
  3. Huang L, Jiang S, Shi Y. Tyrosine kinase inhibitors for solid tumors in the past 20 years (2001–2020). J Hematol Oncol 2020;13(1):143. DOI: 10.1186/s13045-020-00977-0.
  4. Puliafito I, Esposito F, Prestifilippo A, et al. Target therapy in thyroid cancer: Current challenge in clinical use of tyrosine kinase inhibitors and management of side effects. Front Endocrinol (Lausanne) 2022;13:860671. DOI: 10.3389/fendo.2022.860671.
  5. Younis E. Oncogenesis of thyroid cancer. Asian Pac J Cancer Prev 2017;18(5):1191–1199. DOI: 10.22034/APJCP.2017.18.5.1191.
  6. Ragazzi M, Ciarrocchi A, Sancisi V, et al. Update on anaplastic thyroid carcinoma: Morphological, molecular, and genetic features of the most aggressive thyroid cancer. Int J Endocrinol 2014;2014:790834. DOI: 10.1155/2014/790834.
  7. Bhattacharya S, Mahato RK, Singh S, et al. Advances and challenges in thyroid cancer: The interplay of genetic modulators, targeted therapies, and AI-driven approaches. Life Sci 2023;332:122110. DOI: 10.1016/j.lfs.2023.122110.
  8. Li Y, Luo Z, Wang X, et al. Design of new drugs for medullary thyroid carcinoma. Front Oncol 2022;12:993725. DOI: 10.3389/fonc.2022.993725.
  9. Lorusso L, Cappagli V, Valerio L, et al. Thyroid cancers: From surgery to current and future systemic therapies through their molecular identities. Int J Mol Sci 2021;22(6):1–24. DOI: 10.3390/ijms22063117.
  10. Mishra P, Laha D, Grant R, et al. Advances in biomarker-driven targeted therapies in thyroid cancer. Cancers (Basel) 13(24):6194. DOI: 10.3390/cancers13246194.
  11. 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.
  12. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer 2013;13(3):184–199. DOI: 10.1038/nrc3431.
  13. Buffet C, Wassermann J, Hecht F, et al. Redifferentiation of radioiodine-refractory thyroid cancers. Endocr Relat Cancer 2020;27(5):R113–R132. DOI: 10.1530/ERC-19-0491.
  14. Buffet C, Allard L, Guillerm E, et al. Detection of BRAFV600E by digital PCR on fine-needle aspirate enables rapid initiation of dabrafenib and trametinib in unresectable anaplastic thyroid carcinoma. Eur J Endocrinol 2022;187(3):K33–K38. DOI: 10.1530/EJE-22-0366.
  15. Shah MH, Wei 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). DOI: 10.1200/JCO.2017.35.15_suppl.6022.
  16. Ho AL, Dedecjus M, Wirth LJ, et al. Selumetinib plus adjuvant radioactive iodine in patients with high-risk differentiated thyroid cancer: A phase III, randomized, placebo-controlled trial (ASTRA). J Clin Oncol 2022;40(17). 1870–1878. DOI: 10.1200/JCO.21.00714.
  17. Brose MS, Worden FP, Newbold KL, et al. Effect of age on the efficacy and safety of lenvatinib in radioiodine-refractory differentiated thyroid cancer in the phase III select trial. J Clin Oncol 2017;35(23):2692–2699. DOI: 10.1200/JCO.2016.71.6472.
  18. Brose MS, Nutting CM, Sherman SI, et al. Rationale and design of decision: A double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer. BMC Cancer 2011;11:349. DOI: 10.1186/1471-2407-11-349.
  19. 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.
  20. Vella V, Soares P, Moon Hong C, et al. Redifferentiation of radioiodine refractory differentiated thyroid cancer for reapplication of I-131 therapy. Front Endocrinol (Lausanne) 2017;8:260. DOI: 10.3389/fendo.2017.00260.
  21. Lamartina L, Anizan N, Dupuy C, et al. Redifferentiation-facilitated radioiodine therapy in thyroid cancer. Endocr Relat Cancer 2021;28(10):T179–T191. DOI: 10.1530/ERC-21-0024.
  22. Kebebew E, Peng M, Reiff E, et al. A phase II trial of rosiglitazone in patients with thyroglobulin-positive and radioiodine-negative differentiated thyroid cancer. Surgery 2006;140(6).
  23. Schwertheim S, Wein F, Lennartz K, et al. Curcumin induces g2/m arrest, apoptosis, nf-κb inhibition, and expression of differentiation genes in thyroid carcinoma cells. J Cancer Res Clin Oncol 2017;143(7).
  24. Yuan J, Guo Y. Targeted therapy for anaplastic thyroid carcinoma: advances and management. Cancers (Basel) 2022;15(1):179. DOI: 10.3390/cancers15010179.
  25. De Leo S, Trevisan M, Fugazzola L. Recent advances in the management of anaplastic thyroid cancer. Curr Opin Endocrinol Diabetes Obes 2023;30(5):259–264. DOI: 10.1097/MED.0000000000000823.
  26. Busaidy NL, Konda B, Wei L, et al. Dabrafenib versus dabrafenib + trametinib in braf-mutated radioactive iodine refractory differentiated thyroid cancer: Results of a randomized, phase 2, open-label multicenter trial. Thyroid 2022;32(10):1184–1192. DOI: 10.1089/thy.2022.0115.
  27. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in trk fusion–positive cancers in adults and children. N Engl J Med 2018;378(8):731–739. DOI: 10.1056/NEJMoa1714448.
  28. 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. DOI: 10.1016/S0140-6736(14)60421-9.
  29. Danilovic DLS, Castro G, Roitberg FSR, et al. Potential role of sorafenib as neoadjuvant therapy in unresectable papillary thyroid cancer. Arch Endocrinol Metab 2018;62(3):370–375. DOI: 10.20945/2359-3997000000046.
  30. 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.
  31. Sherman SI. Evolution of targeted therapies for thyroid carcinoma. Trans Am Clin Climatol Assoc 2019;130:255–265.
  32. Højer Wang L, Wehland M, Wise PM, et al. Cabozantinib, vandetanib, pralsetinib and selpercatinib as treatment for progressed medullary thyroid cancer with a main focus on hypertension as adverse effect. Int J Mol Sci 2023;24(3):2312. DOI: 10.3390/ijms24032312.
  33. Okafor C, Hogan J, Raygada M, et al. Update on targeted therapy in medullary thyroid cancer. Front Endocrinol (Lausanne) 2021;12:708949. DOI: 10.3389/fendo.2021.708949.
  34. Ma LX, Espin-Garcia O, Bedard PL, et al. Clinical application of next-generation sequencing in advanced thyroid cancers. Thyroid 2022;32(6):657–666. DOI: 10.1089/thy.2021.0542.
  35. Skaugen JM, Taneja C, Liu JB, et al. Performance of a multigene genomic classifier in thyroid nodules with suspicious for malignancy cytology. Thyroid 2022;32(12):1500–1508. DOI: 10.1089/thy.2022.0282.
  36. Alzumaili B, Sadow PM. Update on molecular diagnostics in thyroid pathology: a review. Genes (Basel) 2023;14(7):1314. DOI: 10.3390/genes14071314.
  37. Kargi AY, Bustamante MP, Gulec S. Genomic profiling of thyroid nodules: current role for thyroseq next-generation sequencing on clinical decision-making. Mol Imaging Radionucl Ther 2017;26(Suppl 1):24–35. DOI: 10.4274/2017.26.suppl.04.
  38. Hamidi S, Hofmann MC, Iyer PC, et al. Review article: new treatments for advanced differentiated thyroid cancers and potential mechanisms of drug resistance. Front Endocrinol (Lausanne) 2023;14: 1176731. DOI: 10.3389/fendo.2023.1176731.
  39. Liu Y, Wang J, Hu X, et al. Radioiodine therapy in advanced differentiated thyroid cancer: Resistance and overcoming strategy. Drug Resist Updat 2023;68:100939. DOI: 10.1016/j.drup.2023. 100939.
  40. Worden F. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer. Ther Adv Med Oncol 2014;6(6):267–279. DOI: 10.1177/1758834014548188.
  41. Bible KC, Kebebew E, Brierley J, et al. 2021 American thyroid association guidelines for management of patients with anaplastic thyroid cancer. Thyroid 2021;31(3):337–386. DOI: 10.1089/thy.2020. 0944.
  42. Dang RP, McFarland D, Le VH, et al. Neoadjuvant therapy in differentiated thyroid cancer. Int J Surg Oncol 2016;2016:3743420. DOI: 10.1155/2016/3743420.
  43. Drug monograph (updated 2024 Feb 2) Elsevier drugs information [Internet] Available at:!contentdrug_monograph.
  44. Faugeras L, Pirson AS, Donckier J, et al. Refractory thyroid carcinoma: Which systemic treatment to use? Ther Adv Med Oncol 2018 Jan 23;10:1758834017752853. DOI: 10.1177/1758834017752853.
  45. Cabanillas ME, Ryder M, Jimenez C. Targeted therapy for advanced thyroid cancer: Kinase inhibitors and beyond. Endocr Rev 2019;40(6):1573–1604. DOI: 10.1210/er.2019-00007.
  46. Waliany S, Sainani KL, Park LS, et al. Increase in blood pressure associated with tyrosine kinase inhibitors targeting vascular endothelial growth factor. JACC CardioOncol 2019;1(1):24–36. DOI: 10.1016/j.jaccao.2019.08.012.
  47. Chung JH. Braf and tert promoter mutations: Clinical application in thyroid cancer. Endocr J 2020;67(6):577–584. DOI: 10.1507/endocrj.EJ20-0063.
  48. Dacosta Byfield SA, Adejoro O, Copher R, et al. Real-World treatment patterns among patients initiating small molecule kinase inhibitor therapies for thyroid cancer in the United States. Adv Ther 2019;36(4):896–915. DOI: 10.1007/s12325-019-0890-6.
  49. Wang JR, Zafereo ME, Dadu R, et al. Complete surgical resection following neoadjuvant dabrafenib plus trametinib in BRAFV600E-mutated anaplastic thyroid carcinoma. Thyroid 2019;29(8):1036–1043. DOI: 10.1089/thy.2019.0133.
  50. Capdevila J, Wirth LJ, Ernst T, et al. PD-1 blockade in anaplastic thyroid carcinoma. J Clin Oncol 2020;38(23):2620–2627. DOI: 10.1200/JCO.19.02727.
  51. Cabanillas ME, Dadu R, Ferrarotto R, et al. Atezolizumab combinations with targeted therapy for anaplastic thyroid carcinoma (ATC). Radiology 2021;298(1):123–132. DOI: 10.1148/radiol.2020201791.
  52. Sherman EJ, Ho AL, Fagin JA, et al. Combination of dabrafenib (DAB) and lapatinib (LAP) for the treatment of BRAF-mutant thyroid cancer. J Clin Oncol 2018;36(15_suppl):6087. DOI: 10.1200/JCO.2018.36.15_suppl.6087.
  53. Wadsley J, Beasley M, Garcez K, et al. Guidelines on the use of systemic therapy in patients with advanced thyroid cancer. Clin Oncol (R Coll Radiol) 2023;35(1):57–64. DOI: 10.1016/j.clon.2022.10.009.
  54. Filetti S, Durante C, Hartl D, et al. Thyroid cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019;30(12):1856–1883. DOI: 10.1093/annonc/mdz400.
  55. Davis S, Ullmann TM, Roman S. Disparities in treatment for differentiated thyroid cancer. Thyroid 2023;33(3):287–293. DOI: 10.1089/thy.2022.0432.
  56. Toro-Tobon D, Brito JP. Treatment aggressiveness for differentiated thyroid cancers varies widely and is influenced by physician's attitude and local practice environment. Clin Thyroidol 2022;34(10):450–452. DOI: 10.1089/ct.2022;34.450–452.
  57. Toro-Tobon D, Loor-Torres R, Duran M, et al. Artificial intelligence in thyroidology: A narrative review of the current applications, associated challenges, and future directions. Thyroid 2023;33(8): 903–917. DOI: 10.1089/thy.2023.0132.
  58. Stefanoudakis D, Kathuria-Prakash N, Sun AW, et al. The potential revolution of cancer treatment with CRISPR technology. Cancers (Basel). 2023;15(6):1813. DOI: 10.3390/cancers15061813.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.