Arenbergerová M, Puzanov I
Dermatovenerologicka klinika, Praha.
Klin Onkol. 2012;25(5):323-8.
The incidence of malignant melanoma is increasing worldwide, despite our best efforts in prevention and early detection. The locally advanced disease may be treated surgically with good results, however, metastatic melanoma is considered to be one of the most therapeutically challenging malignancies. The increasing knowledge of molecular changes in melanoma may change this picture. Malignant melanoma is not a singular, homogeneous disease but rather a mixture of subtypes characterized by specific mutations. Tumors with C-KIT mutation respond to therapy with C-KIT kinase inhibitor imatinib and the ones characterized by BRAF mutations respond to BRAF kinase inhibitor vemurafenib. Vemurafenib was approved by US FDA in 2011 and EMA in 2012 for therapy of patients with advanced melanoma, harboring mutation in BRAFV600E gene. Ipilimumab, an antibody to cytotoxic T-lymphocyte antigen 4 (CTLA-4), was registered in 2011 by both US FDA and European Medicines Agency for treatment of metastatic melanoma. This therapy promotes the anti-tumor T-cell activity by blocking a CTLA-4 antigen, a key negative regulator of immune response.
尽管我们在预防和早期检测方面已竭尽全力，但全球恶性黑色素瘤的发病率仍在上升。局部晚期疾病可通过手术治疗并取得良好效果，然而，转移性黑色素瘤被认为是治疗难度最大的恶性肿瘤之一。对黑色素瘤分子变化的认识不断增加可能会改变这种局面。恶性黑色素瘤不是一种单一的、同质的疾病，而是由特定突变特征的亚型混合物。携带C-KIT突变的肿瘤对C-KIT激酶抑制剂伊马替尼治疗有反应，而以BRAF突变为特征的肿瘤对BRAF激酶抑制剂维莫非尼有反应。维莫非尼于2011年获得美国食品药品监督管理局（US FDA）批准，并于2012年获得欧洲药品管理局（EMA）批准，用于治疗携带BRAFV600E基因突变的晚期黑色素瘤患者。伊匹单抗是一种针对细胞毒性T淋巴细胞抗原4（CTLA-4）的抗体，于2011年由美国食品药品监督管理局和欧洲药品管理局注册，用于治疗转移性黑色素瘤。这种疗法通过阻断CTLA-4抗原（免疫反应的关键负调节因子）来促进抗肿瘤T细胞活性。
