分子靶向治疗在恶性黑色素瘤中的应用  

Molecular targeted therapy in malignant melanoma

作　　者：缪秋菊 王逸飞 徐秀莲 Miao Qiuju;Wang Yifei;Xu Xiulian(Department of Pathology,Dermatology Hospital of Chinese Academy of Medical Sciences,Nanjing 210042,China)

机构地区：[1]中国医学科学院皮肤病医院病理科,南京210042

出　　处：《国际肿瘤学杂志》2018年第11期699-702,共4页Journal of International Oncology

基　　金：国家自然科学基金(81772916);江苏省自然科学基金(BK2012505、BK20171132).

摘　　要：恶性黑色素瘤是最常见的致死性皮肤肿瘤。分子靶向治疗药物对晚期或转移性黑色素瘤疗效显著,包括丝裂原活化蛋白激酶(MAPK)抑制剂、磷酯酰肌醇3-激酶(PI3K)抑制剂、酪氨酸激酶受体(TKR)抑制剂和血管内皮生长因子(VEGF)等上调细胞因子的抑制剂。以维莫非尼和达拉非尼为代表的鼠类肉瘤滤过性病毒致癌基因同源体B1(BRAF)激酶抑制剂在黑色素瘤治疗中发挥重要作用,但原发性耐药或获得性耐药的产生,使其临床应用受到一定限制。然而目前以曲美替尼为代表的丝裂原活化细胞外信号调节激酶(MEK)抑制剂等新靶点药物开始应用于临床并呈现出良好的疗效。对耐药机制和多靶点联合用药的研究也为恶性黑色素瘤个体化分子靶向治疗提供了更多可能。Malignant melanoma is the most common fatal skin tumor. Molecular targeted drugs effect on advanced and metastatic melanoma is remarkable, including mitogen-activated protein kinase (MAPK) inhibitors, phosphatidylinositide 3-kinase (PI3K) inhibitors, receptor tyrosine kinase (TKR) inhibitors and vascular endothelial growth factor (VEGF) inhibitors. Vemurafenib and Dabrafenib, as the representative of the v-Raf murine sarcoma viral oncogene homolog B1 (BARF) kinase inhibitors, play important roles for malignant melanoma. However, the primary or acquired drug resistance to this drug limits its clinical use. At present, some new molecular targeted drugs such as Trametinib, representative of mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors, have been used and patients can benefit from the treatment. Studies on the mechanism of drug resistance and the combination of multiple target drugs also provide more potential for individualized molecular targeted therapy of malignant melanoma.

关 键 词：黑色素瘤 药物疗法 酶抑制剂 抗药性 

分 类 号：R739.5[医药卫生—肿瘤]