Tagliaferri Pierosandro, Caraglia Michele, Budillon Alfredo, Marra Monica, Vitale Giovanni, Viscomi Caterina, Masciari Serena, Tassone Pierfrancesco, Abbruzzese Alberto, Venuta Salvatore
Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia di Catanzaro, Via T. Campanella 115, 88100 Catanzaro, Italy.
Cancer Immunol Immunother. 2005 Jan;54(1):1-10. doi: 10.1007/s00262-004-0549-1.
Interferon alpha (IFN-alpha) has been widely used in the treatment of human solid and haematologic malignancies. Although the antitumour activity of IFN-alpha is well recognised at present, no major advances have been achieved in the last few years. Recent findings have provided new information on the molecular mechanisms of the antitumour activity of the cytokine. In fact, IFN-alpha appears to block cell proliferation, at least in part, through the induction of apoptotic effects. This cytokine can also regulate the progression of tumour cells through the different phases of the cell cycle inducing an increase of the expression of the cyclin-dependent kinase inhibitors p21 and p27. However, it must be considered that IFN-alpha is a physiologic molecule with ubiquitously expressed receptors that is likely to activate survival mechanisms in the cell. We have recently identified an epidermal growth factor (EGF) Ras-dependent protective response to the apoptosis induced by IFN-alpha in epidermoid cancer cells. The identification of tissue- and/or tumour-specific survival pathways and their selective targeting might provide a new approach to improve the efficacy of IFN-alpha-based treatment of human cancer. Moreover, new pegylated species of IFN-alpha are now available with a more favourable pharmacokinetic profile. We will review these achievements, and we will specifically address the topic of IFN-alpha-based molecularly targeted combinatory antitumour approaches.
干扰素α（IFN-α）已广泛应用于人类实体瘤和血液系统恶性肿瘤的治疗。尽管目前IFN-α的抗肿瘤活性已得到充分认可，但在过去几年中并未取得重大进展。最近的研究结果为这种细胞因子抗肿瘤活性的分子机制提供了新信息。事实上，IFN-α似乎至少部分地通过诱导凋亡效应来阻断细胞增殖。这种细胞因子还可以通过细胞周期的不同阶段调节肿瘤细胞的进展，诱导细胞周期蛋白依赖性激酶抑制剂p21和p27的表达增加。然而，必须认识到IFN-α是一种生理分子，其受体广泛表达，可能会激活细胞中的存活机制。我们最近在表皮样癌细胞中发现了一种表皮生长因子（EGF）依赖Ras的对IFN-α诱导凋亡的保护性反应。鉴定组织和/或肿瘤特异性存活途径及其选择性靶向可能为提高基于IFN-α的人类癌症治疗疗效提供一种新方法。此外，现在有了具有更有利药代动力学特征的新型聚乙二醇化IFN-α制剂。我们将回顾这些成果，并特别讨论基于IFN-α的分子靶向联合抗肿瘤方法这一主题。
