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α-干扰素(interferon-α,IFN-α)是一种重要的治疗性细胞因子,通过调节细胞周期、抑制原癌基因、调控细胞黏附和血管生成等机制发挥抗肿瘤效应。然而患者对IFN-α反应性的差异限制了其在临床的广泛使用。信号转导通路中一些关键因子如STAT1、STAT3、P48、SOCS1等的异常表达,与肿瘤的IFN-α抗性机制相关;某些原癌基因Bcl-2、c-myc、EVI-1等的过度表达也参与IFN-α抗性形成;此外DNA甲基转移酶、组蛋白修饰与肿瘤IFN-α抗性的发生密切相关。因此,对这些预测IFN-α临床疗效有潜在价值的分子标志物进行多因素分析,选择适合IFN-α治疗的敏感病例,设计个体化的治疗方案,将成为今后肿瘤治疗的一个发展方向。
Interferon-α (IFN-α) is an important therapeutic cytokine that exerts anti-tumor effects by regulating cell cycle, inhibiting oncogene, regulating cell adhesion and angiogenesis. However, the differences in patient response to IFN-α have limited their widespread use in the clinic. The abnormal expression of some key factors such as STAT1, STAT3, P48 and SOCS1 in the signal transduction pathway is related to the mechanism of IFN-α resistance in tumor cells. Some of the oncogenes Bcl-2, c-myc, EVI- Overexpression is also involved in the formation of IFN-αresistance; In addition, DNA methyltransferase, histone modification and tumor IFN-α resistance are closely related. Therefore, the multivariate analysis of these molecular markers predicting the clinical efficacy of IFN-α and the selection of sensitive cases suitable for IFN-α therapy and the design of individualized treatment regimens will become a trend of future cancer treatment.