酪氨酸激酶抑制剂在恶性黑素瘤分子靶向治疗中的进展

Tyrosine kinase inhibitors in molecular targeted therapy of malignant melanoma

恶性黑素瘤是一种异质性肿瘤,不同发病部位或不同组织学类型,可能存在不同的基因和信号转导途径的异常.因此,针对异常基因、信号通路的靶向治疗药物的发明和临床应用为晚期黑素瘤患者的个性化治疗提供了新的选择.中国人最常见的黑素瘤是肢端型,该型黑素瘤中最常见的异常基因是c-kit基因.针对c-kit基因的靶向药物酪氨酸激酶抑制剂在治疗晚期黑素瘤方面已有较多体外研究及临床观察.主要介绍酪氨酸激酶抑制剂中的受体酪氨酸激酶抑制剂、多靶点酪氨酸激酶抑制剂和非受体酪氨酸激酶抑制剂3类药物的药理作用机制及国内外治疗黑素瘤的研究进展,以及酪氨酸激酶抑制剂的常见不良反应.

Malignant melanoma is a heterologous tumor,and abnormalities in different genes and signal transduction pathways may result in malignant melanoma at different body sites and of different histopathological types.Development and clinical application of drugs targeting abnormal genes and signaling pathways provide new options for individualized treatment of patients with advanced melanoma.Acral melanoma is the most common type of melanoma in Chinese population,and c-kit gene is the most common abnormal gene in acral melanoma.There have been many in vitro studies and clinical observations on tyrosine kinase inhibitors （TKIs） targeting the c-kit gene for the treatment of patients with advanced melanoma.This review mainly introduces pharmacologic actions of 3 types of TKIs,including receptor TKIs,multitargeted TKIs and nonreceptor TKIs,as well as domestic and international advances in melanoma therapy and common adverse reactions to TKIs.