葡萄膜黑色素瘤抗血管生成靶向治疗的研究进展_Chinese Journal of Ocular Fundus Diseases

Authors：

曾蕊 ,  李文生

325027 温州医学院附属眼视光医院(曾蕊, 现在成都爱迪眼科医院; 李文生, 现在厦门大学附属厦门眼科中心);

Corresponding author：

李文生, Email: drlws@163.net

Keywords：

葡萄膜肿瘤/药物疗法; 分子靶向治疗; 综述

DOI：

10.3760/cma.j.issn.1005-1015.2014.04.029

Video：

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放射治疗、手术切除、经瞳孔温热疗法、巩膜敷贴治疗、化学药物治疗、免疫治疗等单独或联合应用对改善葡萄膜黑色素瘤(UM)患者生存率无明显差异。抗血管内皮生长因子(VEGF)抑制剂等抗血管生成靶向治疗与化学药物治疗、放射治疗等联合应用可明显提高疗效。但单独使用抗VEGF治疗UM效果并不理想, 而且还存在VEGF抑制剂导致肿瘤形成和转移播散的风险。虽然UM的抗血管生成靶向治疗取得了一些进展, 但是离真正的临床应用还有相当长的距离。需要进一步加强对UM的发病机制研究, 特别是UM新生血管发生发展机制方面的研究, 探索可能的干预靶点; 同时加强UM的转化医学研究, 筛选靶向治疗UM的新药物、新方法。

Citation： 曾蕊, 李文生. 葡萄膜黑色素瘤抗血管生成靶向治疗的研究进展. Chinese Journal of Ocular Fundus Diseases, 2014, 30(4): 428-431. doi: 10.3760/cma.j.issn.1005-1015.2014.04.029 Copy

1.	Munzenrider JE. Uveal melanomas: conservation treatment[J]. Hematol Oncol Clin North Am, 2001, 15:389-402.
2.	魏文斌, 田蓓, 王凤华, 等.影响葡萄膜黑色素瘤局部切除手术治疗预后的多因素分析[J].中华眼底病杂志, 2006, 22:154-156.
3.	周金琼, 魏文斌.葡萄膜黑色素瘤治疗方案的选择对预后的影响[J].国际眼科纵览, 2009, 33:404-410.
4.	Margo CE. The Collaborative Ocular Melanoma Study: an overview[J]. Cancer Control, 2004, 11:304-309.
5.	Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: Ⅴ. Twelve-year mortality rates and prognostic factors: COMS report No. 28[J]. Arch Ophthalmol, 2006, 124:1684-1693.
6.	Virgili G, Gatta G, Ciccolallo L, et al. Survival in patients with uveal melanoma in Europe[J]. Arch Ophthalmol, 2008, 126:1413-1418.
7.	Robertson DM. Changing concepts in the management of choroidal melanoma[J]. Am J Ophthalmol, 2003, 136:161-170.
8.	Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer[J]. N Engl J Med, 2004, 350:2335-2342.
9.	Traina TA, Rugo HS, Dickler M. Bevacizumab for advanced breast cancer[J]. Hematol Oncol Clin North Am, 2007, 21:303-319.
10.	Mäkitie T, Summanen P, Tarkkanen A, et al. Microvascular density in predicting survival of patients with choroidal and ciliary body melanoma[J]. Invest Ophthalmol Vis Sci, 1999, 40:2471-2480.
11.	el Filali M, van der Velden PA, Luyten GPM, et al. Anti-angiogenic therapy in uveal melanoma[J]. Dev Ophthalmol, 2012, 49:117-136.
12.	Sun B, Zhang D, Zhang S, et al. Hypoxia influences vasculogenic mimicry channel formation and tumor invasion-related protein expression in melanoma[J]. Cancer Lett, 2007, 249:188-197.
13.	Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry[J]. Am J Pathol, 1999, 155:739-752.
14.	Brychtova S, Bezdekova M, Brychta T, et al. The role of vascular endothelial growth factors and their receptors in malignant melanomas[J]. Neoplasma, 2008, 55:273-279.
15.	Missotten GS, Notting IC, Schlingemann RO, et al. Vascular endothelial growth factor a in eyes with uveal melanoma[J]. Arch Ophthalmol, 2006, 124:1428-1434.
16.	Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis[J]. J Clin Oncol, 2005, 23:1011-1027.
17.	Ferrara N. Vascular endothelial growth factor: basic science and clinical progress[J]. Endocr Rev, 2004, 25:581-611.
18.	Brown LF, Guidi AJ, Schnitt SJ, et al. Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast[J]. Clin Cancer Res, 1999, 5:1041-1056.
19.	Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch[J]. Nat Rev Cancer, 2003, 3:401-410.
20.	Yang H, Jager MJ, Grossniklaus HE. Bevacizumab suppression of establishment of micrometastases in experimental ocular melanoma[J]. Invest Ophthalmol Vis Sci, 2010, 51:2835-2842.
21.	Stitt AW, Simpson DAC, Boocock C, et al. Expression of vascular endothelial growth factor (VEGF) and its receptors is regulated in eyes with intra-ocular tumours[J]. J Pathol, 1998, 186:306-312.
22.	Crosby MB, Yang H, Gao W, et al. Serum vascular endothelial growth factor (VEGF) levels correlate with number and location of micrometastases in a murine model of uveal melanoma[J]. Br J Ophthalmol, 2011, 95:112-117.
23.	Barak V, Pe'er J, Kalickman I, et al. VEGF as a biomarker for metastatic uveal melanoma in humans[J]. Curr Eye Res, 2011, 36:386-390.
24.	el Filali M, Missotten GS, Maat W, et al. Regulation of VEGF-A in uveal melanoma[J]. Invest Ophthalmol Vis Sci, 2010, 51:2329-2337.
25.	Baserga R. The insulin-like growth factor Ⅰ receptor: a key to tumor growth?[J]. Cancer Res, 1995, 55:249-252.
26.	Slomiany MG, Rosenzweig SA. IGF-1-induced VEGF and IGFBP-3 secretion correlates with increased HIF-1α expression and activity in retinal pigment epithelial cell line D407[J]. Invest Ophthalmol Vis Sci, 2004, 45:2838-2847.
27.	Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors[J]. Nat Med, 2003, 9:669-676.
28.	Sheidow TG, Hooper PL, Crukley C, et al. Expression of vascular endothelial growth factor in uveal melanoma and its correlation with metastasis[J]. Br J Ophthalmol, 2000, 84:750-756.
29.	Bentink S, Haibe-Kains B, Risch T, et al. Angiogenic mRNA and microRNA gene expression signature predicts a novel subtype of serous ovarian cancer[J/OL]. PLoS One, 2012, 7:e30269[2014-06-28]. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030269.
30.	Soni S, Lee DS, DiVito J Jr, et al. Treatment of pediatric ocular melanoma with high-dose interleukin-2 and thalidomide[J]. J Pediatr Hematol Oncol, 2002, 24:488-491.
31.	Masferrer JL, Leahy KM, Koki AT, et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors[J]. Cancer Res, 2000, 60:1306-1311.
32.	Tarnawski AS, Jones MK. Inhibition of angiogenesis by NSAIDs: molecular mechanisms and clinical implications[J]. J Mol Med (Berl), 2003, 81:627-636.
33.	Raut CP, Nawrocki S, Lashinger LM, et al. Celecoxib inhibits angiogenesis by inducing endothelial cell apoptosis in human pancreatic tumor xenografts[J]. Cancer Biol Ther, 2004, 3:1217-1224.
34.	秦岭, 郑钦象, 陈浩, 等.吲哚美辛对脉络膜黑色素瘤细胞增生活性的影响及作用机制[J].中华眼底病杂志, 2011, 27:42-47.
35.	Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis[J]. Am J Physiol Cell Physiol, 2001, 280:1358-1366.
36.	李敏, 陈浩, 秦岭, 等.抗血管内皮生长因子单克隆抗体Bevacizumab对实验性脉络膜黑色素瘤生长的影响[J].中华眼底病杂志, 2011, 27:37-41.
37.	Yang H, Xu Z, Iuvone PM, et al. Angiostatin decreases cell migration and vascular endothelium growth factor (VEGF) to pigment epithelium derived factor (PEDF) RNA ratio in vitro and in a murine ocular melanoma model[J]. Mol Vis, 2006, 12:511-517.
38.	Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis[J]. Cancer Res, 2004, 64:7099-7109.
39.	Mangiameli DP, Blansfield JA, Kachala S, et al. Combination therapy targeting the tumor microenvironment is effective in a model of human ocular melanoma[J/OL]. J Transl Med, 2007, 5:38[2014-06-28]. http://www.translational-medicine.com/content/5/1/38.
40.	王晓光, 罗荣城.抗肿瘤新生血管靶向治疗进展[J].临床肿瘤学杂志, 2006, 11:155-158.
41.	Yang H, Grossniklaus HE. Constitutive overexpression of pigment epithelium-derived factor inhibition of ocular melanoma growth and metastasis[J]. Invest Ophthalmol Vis Sci, 2010, 51:28-34.
42.	Augsburger JJ, Corrêa ZM, Shaikh AH. Effectiveness of treatments for metastatic uveal melanoma[J]. Am J Ophthalmol, 2009, 148:119-127.

1. Munzenrider JE. Uveal melanomas: conservation treatment[J]. Hematol Oncol Clin North Am, 2001, 15:389-402.
2. 魏文斌, 田蓓, 王凤华, 等.影响葡萄膜黑色素瘤局部切除手术治疗预后的多因素分析[J].中华眼底病杂志, 2006, 22:154-156.
3. 周金琼, 魏文斌.葡萄膜黑色素瘤治疗方案的选择对预后的影响[J].国际眼科纵览, 2009, 33:404-410.
4. Margo CE. The Collaborative Ocular Melanoma Study: an overview[J]. Cancer Control, 2004, 11:304-309.
5. Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: Ⅴ. Twelve-year mortality rates and prognostic factors: COMS report No. 28[J]. Arch Ophthalmol, 2006, 124:1684-1693.
6. Virgili G, Gatta G, Ciccolallo L, et al. Survival in patients with uveal melanoma in Europe[J]. Arch Ophthalmol, 2008, 126:1413-1418.
7. Robertson DM. Changing concepts in the management of choroidal melanoma[J]. Am J Ophthalmol, 2003, 136:161-170.
8. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer[J]. N Engl J Med, 2004, 350:2335-2342.
9. Traina TA, Rugo HS, Dickler M. Bevacizumab for advanced breast cancer[J]. Hematol Oncol Clin North Am, 2007, 21:303-319.
10. Mäkitie T, Summanen P, Tarkkanen A, et al. Microvascular density in predicting survival of patients with choroidal and ciliary body melanoma[J]. Invest Ophthalmol Vis Sci, 1999, 40:2471-2480.
11. el Filali M, van der Velden PA, Luyten GPM, et al. Anti-angiogenic therapy in uveal melanoma[J]. Dev Ophthalmol, 2012, 49:117-136.
12. Sun B, Zhang D, Zhang S, et al. Hypoxia influences vasculogenic mimicry channel formation and tumor invasion-related protein expression in melanoma[J]. Cancer Lett, 2007, 249:188-197.
13. Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry[J]. Am J Pathol, 1999, 155:739-752.
14. Brychtova S, Bezdekova M, Brychta T, et al. The role of vascular endothelial growth factors and their receptors in malignant melanomas[J]. Neoplasma, 2008, 55:273-279.
15. Missotten GS, Notting IC, Schlingemann RO, et al. Vascular endothelial growth factor a in eyes with uveal melanoma[J]. Arch Ophthalmol, 2006, 124:1428-1434.
16. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis[J]. J Clin Oncol, 2005, 23:1011-1027.
17. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress[J]. Endocr Rev, 2004, 25:581-611.
18. Brown LF, Guidi AJ, Schnitt SJ, et al. Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast[J]. Clin Cancer Res, 1999, 5:1041-1056.
19. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch[J]. Nat Rev Cancer, 2003, 3:401-410.
20. Yang H, Jager MJ, Grossniklaus HE. Bevacizumab suppression of establishment of micrometastases in experimental ocular melanoma[J]. Invest Ophthalmol Vis Sci, 2010, 51:2835-2842.
21. Stitt AW, Simpson DAC, Boocock C, et al. Expression of vascular endothelial growth factor (VEGF) and its receptors is regulated in eyes with intra-ocular tumours[J]. J Pathol, 1998, 186:306-312.
22. Crosby MB, Yang H, Gao W, et al. Serum vascular endothelial growth factor (VEGF) levels correlate with number and location of micrometastases in a murine model of uveal melanoma[J]. Br J Ophthalmol, 2011, 95:112-117.
23. Barak V, Pe'er J, Kalickman I, et al. VEGF as a biomarker for metastatic uveal melanoma in humans[J]. Curr Eye Res, 2011, 36:386-390.
24. el Filali M, Missotten GS, Maat W, et al. Regulation of VEGF-A in uveal melanoma[J]. Invest Ophthalmol Vis Sci, 2010, 51:2329-2337.
25. Baserga R. The insulin-like growth factor Ⅰ receptor: a key to tumor growth?[J]. Cancer Res, 1995, 55:249-252.
26. Slomiany MG, Rosenzweig SA. IGF-1-induced VEGF and IGFBP-3 secretion correlates with increased HIF-1α expression and activity in retinal pigment epithelial cell line D407[J]. Invest Ophthalmol Vis Sci, 2004, 45:2838-2847.
27. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors[J]. Nat Med, 2003, 9:669-676.
28. Sheidow TG, Hooper PL, Crukley C, et al. Expression of vascular endothelial growth factor in uveal melanoma and its correlation with metastasis[J]. Br J Ophthalmol, 2000, 84:750-756.
29. Bentink S, Haibe-Kains B, Risch T, et al. Angiogenic mRNA and microRNA gene expression signature predicts a novel subtype of serous ovarian cancer[J/OL]. PLoS One, 2012, 7:e30269[2014-06-28]. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030269.
30. Soni S, Lee DS, DiVito J Jr, et al. Treatment of pediatric ocular melanoma with high-dose interleukin-2 and thalidomide[J]. J Pediatr Hematol Oncol, 2002, 24:488-491.
31. Masferrer JL, Leahy KM, Koki AT, et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors[J]. Cancer Res, 2000, 60:1306-1311.
32. Tarnawski AS, Jones MK. Inhibition of angiogenesis by NSAIDs: molecular mechanisms and clinical implications[J]. J Mol Med (Berl), 2003, 81:627-636.
33. Raut CP, Nawrocki S, Lashinger LM, et al. Celecoxib inhibits angiogenesis by inducing endothelial cell apoptosis in human pancreatic tumor xenografts[J]. Cancer Biol Ther, 2004, 3:1217-1224.
34. 秦岭, 郑钦象, 陈浩, 等.吲哚美辛对脉络膜黑色素瘤细胞增生活性的影响及作用机制[J].中华眼底病杂志, 2011, 27:42-47.
35. Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis[J]. Am J Physiol Cell Physiol, 2001, 280:1358-1366.
36. 李敏, 陈浩, 秦岭, 等.抗血管内皮生长因子单克隆抗体Bevacizumab对实验性脉络膜黑色素瘤生长的影响[J].中华眼底病杂志, 2011, 27:37-41.
37. Yang H, Xu Z, Iuvone PM, et al. Angiostatin decreases cell migration and vascular endothelium growth factor (VEGF) to pigment epithelium derived factor (PEDF) RNA ratio in vitro and in a murine ocular melanoma model[J]. Mol Vis, 2006, 12:511-517.
38. Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis[J]. Cancer Res, 2004, 64:7099-7109.
39. Mangiameli DP, Blansfield JA, Kachala S, et al. Combination therapy targeting the tumor microenvironment is effective in a model of human ocular melanoma[J/OL]. J Transl Med, 2007, 5:38[2014-06-28]. http://www.translational-medicine.com/content/5/1/38.
40. 王晓光, 罗荣城.抗肿瘤新生血管靶向治疗进展[J].临床肿瘤学杂志, 2006, 11:155-158.
41. Yang H, Grossniklaus HE. Constitutive overexpression of pigment epithelium-derived factor inhibition of ocular melanoma growth and metastasis[J]. Invest Ophthalmol Vis Sci, 2010, 51:28-34.
42. Augsburger JJ, Corrêa ZM, Shaikh AH. Effectiveness of treatments for metastatic uveal melanoma[J]. Am J Ophthalmol, 2009, 148:119-127.

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葡萄膜黑色素瘤抗血管生成靶向治疗的研究进展

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