Gleave Martin, Miyake Hideake, Zangemeister-Wittke Uwe, Jansen Burkhard
The Prostate Centre, Vancouver General Hospital, Division of Urology, University of British Columbia, Canada.
Cancer Metastasis Rev. 2002;21(1):79-92. doi: 10.1023/a:1020172424152.
Recent technological advances now allowing both large scale data generation and its in-depth analysis have opened new avenues to identify and target genes involved in neoplastic transformation and tumor progression. This accelerated identification and characterization of cancer-relevant molecular targets has sparked considerable interest in the development of new generations of anti-cancer agents. It is anticipated, that these agents will show enhanced specificity for malignant cells and a more favorable side-effect profile due to well-defined and tailored modes of action. Antisense oligonucleotides (ASOs) are short synthetic stretches of chemically modified DNA capable of specifically hybridizing to the mRNA of a chosen cancer-relevant target gene are close, after decades of challenges, close to fulfilling their promise in the clinical setting. Emerging clinical evidence supports the notion that ASOs stand a realistic chance of developing into one of the main players of rationally designed anti-cancer agents, although certainly not all of the challenges have been met to date. The status of antisense targeting of genes relevant to prostate cancer, including bcl-2, bcl-xL, clusterin, androgen receptor (AR) and IGFBPs, are reviewed.
近期的技术进步使得大规模数据生成及其深入分析成为可能,为识别和靶向参与肿瘤转化及肿瘤进展的基因开辟了新途径。癌症相关分子靶点的快速识别与表征激发了人们对新一代抗癌药物研发的浓厚兴趣。预计这些药物将因明确且量身定制的作用方式而对恶性细胞表现出更高的特异性以及更良好的副作用特征。反义寡核苷酸(ASOs)是化学修饰的短链合成DNA,能够与选定的癌症相关靶基因的mRNA特异性杂交,历经数十年挑战后,已接近在临床环境中实现其承诺。新出现的临床证据支持这样一种观点,即反义寡核苷酸有切实机会发展成为合理设计的抗癌药物的主要参与者之一,尽管目前并非所有挑战都已得到解决。本文综述了与前列腺癌相关基因(包括bcl-2、bcl-xL、簇集蛋白、雄激素受体(AR)和胰岛素样生长因子结合蛋白(IGFBPs))的反义靶向研究现状。