[1]何蕊,朱高红.甲状腺髓样癌靶向治疗的研究进展[J].国际放射医学核医学杂志,2018,(2):154-160.[doi:10.3760/cma.j.issn.1673-4114.2018.02.010]
 He Rui,Zhu Gaohong.Research status of medullary thyroid carcinoma targeted therapy[J].International Journal of Radiation Medicine and Nuclear Medicine,2018,(2):154-160.[doi:10.3760/cma.j.issn.1673-4114.2018.02.010]
点击复制

甲状腺髓样癌靶向治疗的研究进展(/HTML)
分享到:

《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
期数:
2018年第2期
页码:
154-160
栏目:
综述
出版日期:
2018-05-09

文章信息/Info

Title:
Research status of medullary thyroid carcinoma targeted therapy
作者:
何蕊 朱高红
650000, 昆明医科大学第一附属医院核医学科
Author(s):
He Rui Zhu Gaohong
Department of Nuclear Medicine, First Affiliated Hospital of Kunming Medical University, Kunming 650000, China
关键词:
甲状腺肿瘤受体表皮生长因子放射性同位素放射疗法分子靶向治疗酪氨酸激酶抑制剂
Keywords:
Thyroid neoplasmsReceptor epidermal growth factorRadioisotopesRadiotherapyMolecular targeted therapyTyrosine kinase inhibitor
DOI:
10.3760/cma.j.issn.1673-4114.2018.02.010
摘要:
甲状腺髓样癌(MTC)是起源于甲状腺C细胞的恶性肿瘤,因其细胞功能的特殊性,治疗主要以及时甲状腺根治性外科手术为首选。但多数患者即使早期也易发生转移,且细胞又缺乏钠碘共同转运体的表达,不能进行放射性碘治疗。近年来,酪氨酸激酶抑制剂靶向治疗的临床应用不断扩大,同时放射性核素靶向治疗及其他靶向治疗正进入一个快速发展的时期,为MTC的治疗带来了契机。笔者重点阐述近年来MTC靶向治疗方面的研究进展。
Abstract:
Medullary thyroid carcinoma (MTC) is a malignant tumor that originated from the C cells of thyroid. Given its special function, timely radical thyroid operation is the preferred treatment for this tumor. However, most patients are prone to early metastasis, and the sodium/iodide symporter is unexpressed on the C cell surface. Therefore, this tumor cannot be treated with radioactive iodine. In recent years, the clinical application of targeted therapy with tyrosine kinase inhibitors is increasing. Furthermore, radionuclide therapy and other interventional targeted therapies are becoming rapidly developed, which results in an opportunity to manage the aggressive medullary thyroid cancer.

参考文献/References:

[1] Pusztaszeri MP, Bongiovanni M, Faquin WC. Update on the cytologic and molecular features of medullary thyroid carcinoma[J]. Adv Anat Pathol,2014,21(1):26-35. DOI:10.1097/PAP.0000000000000004.
[2] Stamatakos M, Paraskeva P, Katsaronis P, et al. Surgical approach to the management of medullary thyroid cancer:when is lymph node dissection needed?[J].Oncology, 2013, 84(6):350-355. DOI:10.1159/000351148.
[3] Kazaure HS, Roman SA, Sosa A. Medullary thyroid microcarcinoma:a population-level analysis of 310 patients[J]. Cancer, 2012, 118(3):620-627. DOI:10.1002/cncr.26283.
[4] Bible KC, Ryder M. Evolving molecularly targeted therapies for advanced-stage thyroid cancers[J]. Nat Rev Clin Oncol, 2016, 13(7):403-416. DOI:10.1038/nrclinonc.2016.19.
[5] NCCN. The NCCN clinical practice guidelines in oncology:thyroid carcinoma(version 2.2017)[EB/OL].[2017-01-02]. http://www.nccn.org/clinicaltrials/physician.html.
[6] Romei C, Ciampi R, Casella F, et al. RET mutation heterogeneity in primary advanced medullary thyroid cancers and their metastases[J]. Oncotarget, 2018, 9(11):9875-9884. DOI:10. 18632/oncotarget.23986.
[7] Takahashi M, Ritz J, Cooper GM. Activation of a novel human transforming gene, ret, by DNA rearrangement[J]. Cell, 1985, 42(2):581-588. DOI:10.1016/0092-8674(85)90115-1.
[8] Pasini B, Hofstra RM, Yin L, et al. The physical map of the human RET proto-oncogene[J]. Oncogene, 1995, 11(9):1737-1743.
[9] Mulligan LM. RET revisited:expanding the oncogenic portfolio[J].Nat Rev Cancer, 2014, 14(3):173-186. DOI:10.1038/nrc3680.
[10] Mohammadi M, Hedayati M. A brief review on the molecular basis of medullary thyroid carcinoma[J]. Cell J, 2017, 18(4):485-492. DOI:10.22074/cellj.2016.4715.
[11] Figlioli G, Landi S, Romei C, et al. Medullary thyroid carcinoma(MTC) and RET, proto-oncogene:Mutation spectrum in the familial cases and a meta-analysis of studies on the sporadic form[J]. Mutat Res, 2013, 752(1):36-44. DOI:10.1016/j.mrrev.2012.09.002.
[12] Capp C, Wajner SM, Siqueira DR, et al. Increased expression of vascular endothelial growth factor and its receptors, VEGFR-1 and VEGFR-2, in medullary thyroid carcinoma[J]. Thyroid, 2010, 20(8):863-871. DOI:10.1089/thy.2009.0417.
[13] Abraham D, Jackson N, Gundara JS, et al. MicroRNA profiling of sporadic and hereditary medullary thyroid cancer identifies predictors of nodal metastasis, prognosis, and potential therapeutic targets[J]. Clin Cancer Res, 2011, 17(14):4772-4781. DOI:10.1158/1078-0432.CCR-11-0242.
[14] Zhu G, Xie L, Miller D. Expression of MicroRNAs in thyroid carcinoma[J]. Methods in Mol Biol, 2017, 1617:261-280. DOI:10.1007/978-1-4939-7046-9_19.
[15] 李寅辉. MicroRNA与甲状腺癌的关系[J].医学综述, 2014, 20(10):1732-1734. DOI:10.3969/j.issn.1006-2084.2014.10.002. Li YH. The relationship between microRNA and thyroid cancer[J]. Med Recapit, 2014, 20(10):1732-1734.
[16] Gundara JS, Zhao JT, Gill AJ, et al. Noncoding RNA blockade of autophagy is therapeutic in medullary thyroid cancer[J]. Cancer Med, 2015, 4(2):174-182. DOI:10.1002/cam4.355.
[17] Zhong WB, Liang YC, Wang CY, et al. Lovastatin suppresses invasiveness of anaplastic thyroid cancer cells by inhibiting Rho geranylgeranylation and RhoA/ROCK signaling[J]. Endocr Relat Cancer, 2005, 12(3):615-629. DOI:10.1677/erc.1.01012.
[18] 汪颖厚, 陈安杰, 王斌, 等. RHOA/ROCK-2信号通路在甲状腺髓样癌中的表达及意义[J].中国医科大学学报, 2014, 43(4):365-367. Wang YH, Chen AJ, Wang B, et al. Expression of RHOA/ROCK-2 signaling pathway in medullary thyroid carcinoma and its clinical significance[J]. J China Med Univ, 2014, 43(4):365-367.
[19] Maxwell JE, Sherman SK, O’dorisio TM. Medical management of metastatic medullary thyroid cancer[J]. Cancer, 2014, 120(21):3287-3301. DOI:10.1002/cncr.28858.
[20] Kim BH, Kim IJ. Recent updates on the management of medullary thyroid carcinoma[J]. Endocrinol Metabo(Seoul), 2016, 31(3):392-399. DOI:10.3803/EnM. 2016.31.3.392.
[21] Wells J, 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]. J Clin Oncol, 2012, 30(2):134-141. DOI:10.1200/JCO.2011.35.5040.
[22] Chau NG, Haddad RI. Vandetanib for the treatment of medullary thyroid cancer[J]. Clin Cancer Res, 2013, 19(3):524-529. DOI:10.1158/1078-0432.CCR-12-2353.
[23] Chatal JF, Kraeber-Bodere F, Goldenberg DM. Treatment of metastatic medullary thyroid cancer with vandetanib:need to stratify patients on basis of calcitonin doubling time[J]. J Clin Oncol, 2012, 30(17):2165. DOI:10.1200/JCO.2012.42.3160.
[24] Tsang VH, Robinson BG, Learoyd DL.The safety of vandetanib for the treatment of thyroid cancer[J]. Expert Opin Drug Saf, 2016,15(8):1107-1113. DOI:10.1080/14740338.2016.1201060.
[25] Bentznen F, Zuzow M, Heald N, et al. In vitro and in vivo activity of cabozantinib(XLl 84), an inhibitor of RET, Met, and VEGFR2, in a model of medullary thyroid cancer[J]. Thyroid, 2013, 23(12):1569-1577. DOI:10.1089/thy. 2013.0137.
[26] Viola D, Cappagli V, Elisei R. Cabozantinib (XL184) for the treatment of locally advanced or metastatic progressive medullary thyroid cancer[J]. Future Oncol, 2013, 9(8):1083-1092. DOI:10.2217/FON.13.128.
[27] Elisei R, Schlumberger MJ, Müller SP, et al. Cabozantinib in progressive medullary thyroid cancer[J]. J Clin Oncol, 2013, 31(29):3639-3646. DOI:10.1200/JCO.2012.48.4659.
[28] 秦建武. 精准医疗在甲状腺癌中的临床应用与展望[J].医学与哲学, 2016, 37(10B):772-1002. DOI:10.12014/j.issn.1002-0772. 2016.10b.03. Qin JW. Clinical application and prospect of precision medicine in thyroid cancer[J]. Med Philos, 2016, 37(10B):772-1002.
[29] Ferrari SM, Politti U, Spisni RA, et al. Sorafenib in the treatment of thyroid cancer[J]. Expert Rev Anticancer Ther, 2015, 15(8):863-874. DOI:10.1586/14737140.2015.1064770.
[30] De Castroneves LA, Negrao MV, Costa De Freitas RM, et al.Sorafenib for the treatment of progressive metastatic medullary thyroid cancer:efficacy and safety analysis[J]. Thyroid, 2016, 26(3):414-419. DOI:10.1089/thy.2015.0334.
[31] Bible KC, Suman VJ, Molina JR, et al. A multicenter international phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma:MC057H[J]. J Clin Endocrinol Metab, 2014, 99(5):1687-1693. DOI:10.1210/jc.2013-3713.
[32] Perri F, Pezzullo L, Chiofalo MG, et al.Targeted therapy:a new hope for thyrold carcinomas[J]. Crit Rev Oncol Hematol, 2015, 94(1):55-63.
[33] Ravaud A, De La Fouchardiere C, Asselineau J, et al. Efficacy of sunitinib in advanced medullary thyroid carcinoma:intermediate results of phase Ⅱ THYSU[J]. Oncologist, 2010, 15(2):212-213. DOI:10.1634/theoncologist. 2009-0303.
[34] Krajewska J, Kukulska A, Jarzab B. Efficacy of lenvatinib in treating thyroid cancer[J]. Expert Opin Pharmacother, 2016, 17(12):1683-1691. DOI:10.1080/14656566.2016.1206078.
[35] Schlumberger M, Jarzab B, Cabanillas ME, et al. A phase Ⅱ trial of the multitargeted tyrosine kinase inhibitor lenvatinib (E7080) in advanced medullary thyroid cancer[J]. Clin Cancer Res, 2016, 22(1):44-53. DOI:10.1158/1078-0432.CCR-15-1127.
[36] Salaun PY, Bodet-Milin C, Frampas E, et al. Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma[J]. Cancer, 2010,116(4 Suppl):1053S-1058. DOI:10.1002/cncr.24792.
[37] Kraeber-Bodéré F, Salaun PY, Ansquer C, et al. Pretargeted radioimmunotherapy (pRAIT) in medullary thyroid cancer (MTC)[J]. Tumour Biol, 2012, 33(3):601-606. DOI:10.1007/s13277-012-0359-6.
[38] Vitale G, Lupoli G, Guarrasi R, et al.Interleukin-2 and lanreotide in the treatment of medullary thyroid cancer:in vitro and in vivo studies[J/OL]. J Clin Endocrinol Metab, 2013, 98(10):E1567-E1574[2017-11-20]. https://academic.oup.com/jcem/article/98/10/E1567/2833347. DOI:10.1210/jc.2013-1443.
[39] He R, Wang H, Zhu GH, et al. Incorporating 131I into a PAMAM(G5.0) dendrimer-conjugate:design of a theranostic nanosensor for medullary thyroid carcinoma[J]. RSC Adv, 2017, 7(26):16181-16188. DOI:10.1039/C7RA00604G.
[40] 陈礼林, 谢丽君, 朱高红, 等. 靶向肽结合131I-PAMAM(G5.0)抑制甲状腺髓样癌细胞增殖的研究[J]. 国际放射医学核医学杂志, 2017, 41(5):307-311. DOI:10.3760/cma.j.issn. 1673-4114. 2017. 05.001. Chen LL, Xie LJ, Zhu GH, et al. Effects of targeted peptide-conjugated 131I-PAMAM(G5.0)on the inhibition of medullary thyroid carcinoma cells proliferation[J]. Inter J Radiat Med Nucl Med, 2017, 41(5):307-311.
[41] 李娟, 甘生敏, 罗超, 等. AG490抑制甲状腺髓样癌TT细胞增殖并提高其放射敏感性[J]. 细胞与分子免疫学杂志, 2015, 31(6):753-757. DOI:10.12423/j.cnki.cjcmi.007416. Li J, Gan SM, Luo C, et al. AG490 inhibits the proliferation of human medullary thyroid carcinoma TT cells and increases their radiosensitivity[J]. J Cell Mol Med, 2015, 31(6):753-757.
[42] Sosonkina N, Starenki D, Park JI. The role of STAT3 in thyroid cancer[J]. Cancers (Basel), 2014, 6(1):526-544. DOI:10.3390/cancers 6010526.
[43] Karen J, Rodriguez A, Friman T, et al. Effects of the histone deacetylase inhibitor valproic acid on human pericytes in vitro[J/OL].PLoS One, 2011, 6(9):e24954[2017-11-20]. http:http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0024954. DOI:10.1371/journal.pone.0024954.
[44] Mannaerts I, Nuytten NR, Rogiers V, et al. Chronic administration of valproic acid inhibits activation of mouse hepatic stellate cells in vitro and in vivo[J]. Hepatology, 2010, 51(2):603-614. DOI:10.1002/hep.23334.
[45] Greenblatt DY, Ma CY, Adler JT, et al. Valproic acid activates Notch 1 signaling and induces apoptosis in medullary thyroid cancer cells[J]. Ann Surg, 2008, 247(6):1036-1040. DOI:10.1097/SLA.0b013e3181758d0e.
[46] Adler JT, Hottinger DG, Kunnimalaiyaan M, et al. Inhibition of growth in medullary thyroid cancer cells with histone deacetylase inhibitors and Lithium chloride[J]. J Surg Res, 2010, 159(2):640-644. DOI:10.1016/j.jss.2008.08.004.
[47] 齐研, 贾慧英. 丙戊酸盐对甲状腺髓样癌TT细胞的影响[J]. 诊断学理论与实践, 2015, 14(3):248-251. DOI:10.16150/j.1671-2870.2015.03.013. Qi Y, Jia HY. Effects of valproic acid on TT human medullary thyroid carcinoma cell line[J]. J Diagn Concepts Pract, 2015,14(3):248-251.
[48] Li LC, Liu GD, Zhang XJ, et al. Autophagy, a novel target for chemotherapeutic intervention of thyroid cancer[J]. Cancer Chemother Pharmacol, 2014, 73(3):439-449. DOI:10.1007/s00280-013-2363-y.
[49] 曹乐薇.自噬与甲状腺癌[J].中国医师杂志, 2016, 18(6):950-953. DOI:10.3760/cma.j.issn. 1008-1372. 2016.06.049. Cao LW. Autophagy and thyroid cancer[J]. J Chin Phys, 2016, 18(6):950-953.
[50] Lin CI, Whang EE, Lorch JH, et al. Autophagic activation potentiates the antiproliferative effects of tyrosine kinase inhibitors in medullary thyroid cancer[J]. Surgery, 2012, 152(6):1142-1149. DOI:10.1016/j.surg. 2012.08.016.

相似文献/References:

[1]梁雯丽,郑艳,李娜,等.Graves甲亢患者131I治疗后早期TRAb及TSAb变化的研究分析[J].国际放射医学核医学杂志,2016,40(1):13.[doi:10.3760/cma.j.issn.1673-4114.2016.01.003]
 Liang Wenli,Zheng Yan,Li Na,et al.Analysis of the changes in early TRAb and TSAb after 131I treatment for patients with Graves hyperthyroidism[J].International Journal of Radiation Medicine and Nuclear Medicine,2016,40(2):13.[doi:10.3760/cma.j.issn.1673-4114.2016.01.003]
[2]邢宇,赵新明.放射性核素标记HER2亲和体分子探针精准诊疗的研究进展[J].国际放射医学核医学杂志,2016,40(2):139.[doi:10.3760/cma.j.issn.1673-4114.2016.02.011]
 Xing Yu,Zhao Xinming.Advances in radionuclide-labeled HER2 affibody molecular probes for precise diagnosis and treatment[J].International Journal of Radiation Medicine and Nuclear Medicine,2016,40(2):139.[doi:10.3760/cma.j.issn.1673-4114.2016.02.011]
[3]李盼丽,宋少莉.碘难治性分化型甲状腺癌靶向药物治疗进展[J].国际放射医学核医学杂志,2016,40(3):202.[doi:10.3760/cma.j.issn.1673-4114.2016.03.009]
 Li Panli,Song Shaoli.Radioactive iodine refractory differentiated thyroid cancer targeted therapy[J].International Journal of Radiation Medicine and Nuclear Medicine,2016,40(2):202.[doi:10.3760/cma.j.issn.1673-4114.2016.03.009]
[4]杨珂,唐波,于夕荣,等.甲状腺癌131i治疗病房的辐射屏蔽计算与评价[J].国际放射医学核医学杂志,2015,39(5):405.[doi:10. 3760 / cma. j. issn. 1673-4114. 2015. 05. 012]
 yang ke,tang bo,yu xirong,et al.shielding calculation and assessment in 131i therapy for thyroid cancer[J].International Journal of Radiation Medicine and Nuclear Medicine,2015,39(2):405.[doi:10. 3760 / cma. j. issn. 1673-4114. 2015. 05. 012]
[5]陈立,陈跃.分化型甲状腺癌骨转移诊断及疗效评价的核素显像研究进展[J].国际放射医学核医学杂志,2016,40(6):452.[doi:10.3760/cma.j.issn.1673-4114.2016.06.010]
 Chen Li,Chen Yue.Diagnosis and evaluation of curative effect progress of radionuclide imaging methods in differentiated thyroid cancer of bone metastases[J].International Journal of Radiation Medicine and Nuclear Medicine,2016,40(2):452.[doi:10.3760/cma.j.issn.1673-4114.2016.06.010]
[6]郭坤,高蕊,于燕,等.表皮生长因子受体基因表达与甲状腺功能亢进症131I治疗预后的关系[J].国际放射医学核医学杂志,2015,39(1):4.[doi:10.3760/cma.j.issn.1673-4114.2015.01.003]
 Guo Kun,Gao Rui,Yu Yan,et al.The relationship between epidermal growth factor receptor mRNA expression and the efficacv of 131I treatment in hyperthyroidism patients[J].International Journal of Radiation Medicine and Nuclear Medicine,2015,39(2):4.[doi:10.3760/cma.j.issn.1673-4114.2015.01.003]
[7]惠金子,赵德善.Tg、TgAb及TSH在分化型甲状腺癌术前的预测分析[J].国际放射医学核医学杂志,2015,39(2):110.[doi:10.3760/cma.j.issn.1673-4114.2015.02.002]
 Hui Jinzi,Zhao Deshan.The prediction of risk of differentiated thyroid carcinoma with preoperative serum thyroid stimulating hormone, thyrogiobulin and antithyroglobulin antibody[J].International Journal of Radiation Medicine and Nuclear Medicine,2015,39(2):110.[doi:10.3760/cma.j.issn.1673-4114.2015.02.002]
[8]刘斌,潘明志.BRAF基因突变对甲状腺乳头状癌诊治价值的研究进展[J].国际放射医学核医学杂志,2015,39(2):154.[doi:10.3760/cma.j.issn.1673-4114.2015.02.011]
 Liu Bin,Pan Mingzhi.Advances in value of BRAF gene mutation on the diagnosis and treatment of papillary thyroid cancer[J].International Journal of Radiation Medicine and Nuclear Medicine,2015,39(2):154.[doi:10.3760/cma.j.issn.1673-4114.2015.02.011]
[9]胡斌,王锦锋,毛秋粉.18F-FDG PET/CT显像在Tg阳性131I全身显像阴性的分化型甲状腺癌患者中的应用价值[J].国际放射医学核医学杂志,2015,39(3):242.[doi:10.3760/cma.j.issn.1673-4114.2015.03.012]
 Hu Bin,Wang Jinfeng,Mao Qiufen.The application value of 18F-FDG PET/CT in patients with differentiated thyroid cancer of high thyroglobulin level and negative 131I whole body scan[J].International Journal of Radiation Medicine and Nuclear Medicine,2015,39(2):242.[doi:10.3760/cma.j.issn.1673-4114.2015.03.012]
[10]刘鹏杰,唐铭,邓智勇,等.131I治疗儿童分化型甲状腺癌期间出现低钙血症伴癫痫发作一例[J].国际放射医学核医学杂志,2015,39(4):352.[doi:10.3760/cma.j.issn.1673-4114.2015.04.017]
[11]程维维,王辉.促甲状腺激素受体与甲状腺癌关系的研究进展[J].国际放射医学核医学杂志,2012,36(2):69.[doi:10.3760/cma.j.issn.1673-4114.2012.02.002]
 CHENG Wei-wei,WANG Hui.Progress in the relationship of thyroid-stimulating hormone receptor and thyroid carcinoma[J].International Journal of Radiation Medicine and Nuclear Medicine,2012,36(2):69.[doi:10.3760/cma.j.issn.1673-4114.2012.02.002]
[12]侯仁花,吕中伟.生长抑素受体显像剂99mTc-depreotide的研究进展[J].国际放射医学核医学杂志,2008,32(1):15.
 HOU Ren-hua,LÜ,Zhong-wei.The progress of a new somatostatin receptor agent 99mTc-depreotide[J].International Journal of Radiation Medicine and Nuclear Medicine,2008,32(2):15.

备注/Memo

备注/Memo:
收稿日期:2017-11-26。
基金项目:国家自然科学基金(81360223)
通讯作者:朱高红,Email:1026909611@qq.com
更新日期/Last Update: 2018-05-09