Lahn Michael M, Sundell Karen L, Paterson Blake M
Eli Lilly and Company, Oncology Product Development, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Oncol Rep. 2004 Feb;11(2):515-22.
Antisense oligonucleotide (ASO) technology offers a novel approach for the development of anti-cancer drugs. For example, the ASO aprinocarsen has been developed to specifically inhibit the intracellular signal transduction protein, protein kinase C-alpha (PKC-alpha). The clinical development of such specific or "new targeted" agents in cancer requires a comprehensive understanding of the target protein. This understanding is expected to improve the identification of patients who most likely will benefit from treatment with a specific inhibitor, such as aprinocarsen. In order to better understand the role of PKC-alpha in nervous system malignancies we here review the published literature on PKC-alpha expression in nervous system tumors, including glioblastoma multiforme. In pre-clinical experiments aprinocarsen had demonstrated anti-tumor activity, in particular in animal models of glioblastoma. Thus, clinical study CS10 with aprinocarsen was undertaken in patients with central nervous system (CNS) malignancies. The results of this study and considerations for future clinical studies in CNS tumors are reviewed.
反义寡核苷酸（ASO）技术为抗癌药物的研发提供了一种新方法。例如，已开发出ASO阿普瑞卡森，以特异性抑制细胞内信号转导蛋白蛋白激酶C-α（PKC-α）。在癌症中开发此类特异性或“新靶向”药物需要全面了解靶蛋白。这种了解有望改善对最有可能从特异性抑制剂（如阿普瑞卡森）治疗中获益的患者的识别。为了更好地理解PKC-α在神经系统恶性肿瘤中的作用，我们在此回顾已发表的关于PKC-α在神经系统肿瘤（包括多形性胶质母细胞瘤）中表达的文献。在临床前实验中，阿普瑞卡森已显示出抗肿瘤活性，特别是在胶质母细胞瘤的动物模型中。因此，对患有中枢神经系统（CNS）恶性肿瘤的患者进行了阿普瑞卡森的CS10临床研究。本文回顾了该研究的结果以及对未来CNS肿瘤临床研究的考虑因素。
