Progress of Molecular Targeted Therapy for Thyroid Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YANGZhong-yuan , WANGXi , LIYin , LIQiu-li , CHENShu-wei , ZHANGQuan ,  GUOZhu-ming

Department of Head and Neck Surgery, Sun Yet-san University Cancer Center, Guangzhou 510060, Guangdong Province, China;

Corresponding author：

GUOZhu-ming, Email: guozhm@sysucc.org.cn

Keywords：

Thyroid cancer; Molecular targeted therapy; Protein kinase inhibitor

DOI：

10.7507/1007-9424.20150209

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review the recent progress of the molecular targeted therapy for thyroid cancer. Methods The literatures of molecular etiology for thyroid cancer, mechanism and evaluation of targeted therapy via Medline and CHKD database were reviewed. Results So far, four molecular targeted drugs (Sorafenib, Lenvatinib, Vandetanib, and Cabozantinib) have been approved for treatment of advanced thyroid cancer by FDA. They can mainly improve the patient's progression-free survival. Besides, several new molecular targeted drugs have accomplishedⅠphase or Ⅱ phase clinical trials. These drugs may be new options for treatment of advanced thyroid cancer in the future. Conclusions Molecular targeted drugs have been the main therapeutic method for advanced thyroid cancer. However, we should invent more effective new drugs and investigate the drug combination to improve the therapeutic effect.

Citation： YANGZhong-yuan, WANGXi, LIYin, LIQiu-li, CHENShu-wei, ZHANGQuan, GUOZhu-ming. Progress of Molecular Targeted Therapy for Thyroid Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(7): 803-809. doi: 10.7507/1007-9424.20150209 Copy

1.	Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg, 2014, 140(4):317-322.
2.	杨雷, 王宁. 甲状腺癌流行病学研究进展. 中华预防医学杂志, 2014, 48(8):744-748.
3.	袁昊绪. 恶性肿瘤仍占北京市民死亡原因首位. 首都医药, 2014, 15:31-32.
4.	李科, 林国桢, 周琴, 等. 2000-2011年广州市城区甲状腺癌的发病趋势分析. 中华预防医学杂志, 2015. 49(2):142-146.
5.	Eustatia-Rutten CF, Corssmit EP, Biermasz NR, et al. Survival and death causes in differentiated thyroid carcinoma. J Clin Endocrinol Metab, 2006, 91(1):313-319.
6.	Durante C, Haddy N, Baudin E, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma:benefits and limits of radioiodine therapy. J Clin Endocrinol Metab, 2006, 91(8):2892-2899.
7.	Elisei R, Ugolini C, Viola D, et al. BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma:a 15-year median follow-up study. J Clin Endocrinol Metab, 2008, 93(10):3943-3949.
8.	Husain M, Alsever RN, Lock JP, et al. Failure of medullary carcinoma of the thyroid to respond to doxorubicin therapy. Horm Res, 1978, 9(1):22-25.
9.	Smallridge RC, Marlow LA, Copland JA. Anaplastic thyroid cancer:molecular pathogenesis and emerging therapies. Endocr Relat Cancer, 2009, 16(1):17-44.
10.	Smith NR, Baker D, James NH, et al. Vascular endothelial growth factor receptors VEGFR-2 and VEGFR-3 are localized primarily to the vasculature in human primary solid cancers. Clin Cancer Res, 2010, 16(14):3548-3561.
11.	Zarebczan B, Chen H. Multi-targeted approach in the treatment of thyroid cancer. Minerva Chir, 2010. 65(1):59-69.
12.	Melillo RM, Castellone MD, Guarino V, et al. The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J Clin Invest, 2005, 115(4):1068-1081.
13.	Knauf JA, Kuroda H, Basu S, et al. RET/PTC-induced dedifferentiation of thyroid cells is mediated through Y1062 signaling through SHC-RAS-MAP kinase. Oncogene, 2003, 22(28):4406-4412.
14.	Nucera C, Porrello A, Antonello ZA, et al. B-Raf (V600E) and thrombospondin-1 promote thyroid cancer progression. Proc Natl Acad Sci USA, 2010, 107(23):10649-10654.
15.	Kroll TG, Sarraf P, Pecciarini L, et al. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma[corrected]. Science, 2000, 289(5483):1357-1360.
16.	Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol, 2011, 7(10):569-580.
17.	Thomas L, Lai SY, Dong W, et al. Sorafenib in metastatic thyroid cancer:a systematic review. Oncologist, 2014, 19(3):251-258.
18.	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.
19.	Zhang L, Zhou Q, Ma L, et al. Meta-analysis of dermatological toxicities associated with sorafenib. Clin Exp Dermatol, 2011, 36(4):344-350.
20.	Azad NS, Aragon-Ching JB, Dahut WL, et al. Hand-foot skin reaction increases with cumulative sorafenib dose and with combination anti-vascular endothelial growth factor therapy. Clin Cancer Res, 2009, 15(4):1411-1416.
21.	Boudou-Rouquette P, Ropert S, Mir O, et al. Variability of sorafenib toxicity and exposure over time:a pharmacokinetic/pharmacodynamic analysis. Oncologist, 2012, 17(9):1204-1212.
22.	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 Ⅲtrial. J Clin Oncol, 2012, 30(2):134-141.
23.	Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. New England Journal of Medicine, 2015, 372(7):621-630.
24.	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.
25.	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.
26.	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.
27.	St Bernard R, Zheng L, Liu W, et al. Fibroblast growth factor receptors as molecular targets in thyroid carcinoma. Endocrinology, 2005, 146(3):1145-1153.
28.	Kurzrock R, Sherman SI, Ball DW, et al. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol, 2011, 29(19):2660-2666.
29.	Karras S, Pontikides N, Krassas GE. Pharmacokinetic evaluation of cabozantinib for the treatment of thyroid cancer. Expert Opin Drug Metab Toxicol, 2013, 9(4):507-515.
30.	Giunti S, Antonelli A, Amorosi A, et al. Cellular signaling pathway alterations and potential targeted therapies for medullary thyroid carcinoma. Int J Endocrinol, 2013, 2013:803171.
31.	Elisei R, Schlumberger MJ, Müller SP, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol, 2013, 31(29):3639-3646.
32.	Patson B, B Cohen R, Olszanski AJ. Pharmacokinetic evaluation of axitinib. Expert Opin Drug Metab Toxicol, 2012, 8(2):259-270.
33.	Hayes DN, Lucas AS, Tanvetyanon T, et al. Phase Ⅱ efficacy and pharmacogenomic study of Selumetinib (AZD6244; ARRY-142886) in iodine-131 refractory papillary thyroid carcinoma with or without follicular elements. Clin Cancer Res, 2012, 18(7):2056-2065.
34.	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.
35.	Wein R, Colombo J. Cabozantinib for progressive metastatic medullary thyroid cancer:a review. Ther Clin Risk Manag, 2014, 10:395-404.
36.	Verbeek HH, Alves MM, de Groot JW, et al. The effects of four different tyrosine kinase inhibitors on medullary and papillary thyroid cancer cells. J Clin Endocrinol Metab, 2011, 96(6):E991E995.
37.	Dadu R, Devine C, Hernandez M, et al. Role of salvage targeted therapy in differentiated thyroid cancer patients who failed first-line sorafenib. J Clin Endocrinol Metab, 2014, 99(6):2086-2094.

1. Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg, 2014, 140(4):317-322.
2. 杨雷, 王宁. 甲状腺癌流行病学研究进展. 中华预防医学杂志, 2014, 48(8):744-748.
3. 袁昊绪. 恶性肿瘤仍占北京市民死亡原因首位. 首都医药, 2014, 15:31-32.
4. 李科, 林国桢, 周琴, 等. 2000-2011年广州市城区甲状腺癌的发病趋势分析. 中华预防医学杂志, 2015. 49(2):142-146.
5. Eustatia-Rutten CF, Corssmit EP, Biermasz NR, et al. Survival and death causes in differentiated thyroid carcinoma. J Clin Endocrinol Metab, 2006, 91(1):313-319.
6. Durante C, Haddy N, Baudin E, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma:benefits and limits of radioiodine therapy. J Clin Endocrinol Metab, 2006, 91(8):2892-2899.
7. Elisei R, Ugolini C, Viola D, et al. BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma:a 15-year median follow-up study. J Clin Endocrinol Metab, 2008, 93(10):3943-3949.
8. Husain M, Alsever RN, Lock JP, et al. Failure of medullary carcinoma of the thyroid to respond to doxorubicin therapy. Horm Res, 1978, 9(1):22-25.
9. Smallridge RC, Marlow LA, Copland JA. Anaplastic thyroid cancer:molecular pathogenesis and emerging therapies. Endocr Relat Cancer, 2009, 16(1):17-44.
10. Smith NR, Baker D, James NH, et al. Vascular endothelial growth factor receptors VEGFR-2 and VEGFR-3 are localized primarily to the vasculature in human primary solid cancers. Clin Cancer Res, 2010, 16(14):3548-3561.
11. Zarebczan B, Chen H. Multi-targeted approach in the treatment of thyroid cancer. Minerva Chir, 2010. 65(1):59-69.
12. Melillo RM, Castellone MD, Guarino V, et al. The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J Clin Invest, 2005, 115(4):1068-1081.
13. Knauf JA, Kuroda H, Basu S, et al. RET/PTC-induced dedifferentiation of thyroid cells is mediated through Y1062 signaling through SHC-RAS-MAP kinase. Oncogene, 2003, 22(28):4406-4412.
14. Nucera C, Porrello A, Antonello ZA, et al. B-Raf (V600E) and thrombospondin-1 promote thyroid cancer progression. Proc Natl Acad Sci USA, 2010, 107(23):10649-10654.
15. Kroll TG, Sarraf P, Pecciarini L, et al. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma[corrected]. Science, 2000, 289(5483):1357-1360.
16. Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol, 2011, 7(10):569-580.
17. Thomas L, Lai SY, Dong W, et al. Sorafenib in metastatic thyroid cancer:a systematic review. Oncologist, 2014, 19(3):251-258.
18. 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.
19. Zhang L, Zhou Q, Ma L, et al. Meta-analysis of dermatological toxicities associated with sorafenib. Clin Exp Dermatol, 2011, 36(4):344-350.
20. Azad NS, Aragon-Ching JB, Dahut WL, et al. Hand-foot skin reaction increases with cumulative sorafenib dose and with combination anti-vascular endothelial growth factor therapy. Clin Cancer Res, 2009, 15(4):1411-1416.
21. Boudou-Rouquette P, Ropert S, Mir O, et al. Variability of sorafenib toxicity and exposure over time:a pharmacokinetic/pharmacodynamic analysis. Oncologist, 2012, 17(9):1204-1212.
22. 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 Ⅲtrial. J Clin Oncol, 2012, 30(2):134-141.
23. Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. New England Journal of Medicine, 2015, 372(7):621-630.
24. 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.
25. 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.
26. 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.
27. St Bernard R, Zheng L, Liu W, et al. Fibroblast growth factor receptors as molecular targets in thyroid carcinoma. Endocrinology, 2005, 146(3):1145-1153.
28. Kurzrock R, Sherman SI, Ball DW, et al. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol, 2011, 29(19):2660-2666.
29. Karras S, Pontikides N, Krassas GE. Pharmacokinetic evaluation of cabozantinib for the treatment of thyroid cancer. Expert Opin Drug Metab Toxicol, 2013, 9(4):507-515.
30. Giunti S, Antonelli A, Amorosi A, et al. Cellular signaling pathway alterations and potential targeted therapies for medullary thyroid carcinoma. Int J Endocrinol, 2013, 2013:803171.
31. Elisei R, Schlumberger MJ, Müller SP, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol, 2013, 31(29):3639-3646.
32. Patson B, B Cohen R, Olszanski AJ. Pharmacokinetic evaluation of axitinib. Expert Opin Drug Metab Toxicol, 2012, 8(2):259-270.
33. Hayes DN, Lucas AS, Tanvetyanon T, et al. Phase Ⅱ efficacy and pharmacogenomic study of Selumetinib (AZD6244; ARRY-142886) in iodine-131 refractory papillary thyroid carcinoma with or without follicular elements. Clin Cancer Res, 2012, 18(7):2056-2065.
34. 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.
35. Wein R, Colombo J. Cabozantinib for progressive metastatic medullary thyroid cancer:a review. Ther Clin Risk Manag, 2014, 10:395-404.
36. Verbeek HH, Alves MM, de Groot JW, et al. The effects of four different tyrosine kinase inhibitors on medullary and papillary thyroid cancer cells. J Clin Endocrinol Metab, 2011, 96(6):E991E995.
37. Dadu R, Devine C, Hernandez M, et al. Role of salvage targeted therapy in differentiated thyroid cancer patients who failed first-line sorafenib. J Clin Endocrinol Metab, 2014, 99(6):2086-2094.

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Progress of Molecular Targeted Therapy for Thyroid Cancer

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