Gleave Martin, Nelson Colleen, Chi Kim
The Prostate Centre at Vancouver General Hospital, Division of Urology, University of British Columbia, D9, 2733 Heather Street, Vancouver, BC, Canada V6H 3Z3.
Curr Drug Targets. 2003 Apr;4(3):209-21. doi: 10.2174/1389450033491190.
The main obstacle to improved survival of advanced prostate cancer is our failure to prevent or treat its progression to its lethal and untreatable stage of androgen independence. New therapeutic agents designed to prevent androgen-independent progression are required. Accelerated identification and characterization of cancer-relevant molecular targets has sparked considerable interest in the development of new generations of anti-cancer agents that specifically inhibit a progression-relevant target. Antisense oligonucleotides, short synthetic stretches of chemically modified DNA capable of specifically hybridizing to the mRNA of a chosen cancer-relevant target gene. promise to show enhanced specificity for malignant cells with a more favorable side-effect profile due to well-defined and tailored modes of action. Although not all of the challenges have been met to date, emerging clinical evidence supports the premise that antisense oligonucleotides stand a realistic chance of emerging as major partners of rationally designed anti-cancer regimens. The status of antisense targeting of several genes, including bcl-2, bcl-xL, clusterin, androgen receptor and IGFBPs, relevant to prostate and other cancers, are reviewed.
晚期前列腺癌患者生存率提高的主要障碍在于，我们未能预防或治疗其进展至雄激素非依赖这一致命且无法治疗的阶段。因此，需要研发旨在预防雄激素非依赖进展的新型治疗药物。癌症相关分子靶点的快速鉴定和表征激发了人们对新一代抗癌药物研发的浓厚兴趣，这些药物能够特异性抑制与进展相关的靶点。反义寡核苷酸是短的化学修饰DNA合成片段，能够与选定的癌症相关靶基因的mRNA特异性杂交。由于其作用模式明确且可定制，有望对恶性细胞表现出更高的特异性，同时副作用更小。尽管目前并非所有挑战都已解决，但新出现的临床证据支持这样一个前提，即反义寡核苷酸很有可能成为合理设计的抗癌方案的主要组成部分。本文综述了针对包括bcl-2、bcl-xL、簇集素、雄激素受体和胰岛素样生长因子结合蛋白等与前列腺癌及其他癌症相关的多个基因的反义靶向研究现状。
