肿瘤的靶向介入治疗  

Targeting intervention for tumor therapy

作　　者：梁伟[1] 王亚芹[2] 刘兴君[1] 

机构地区：[1]中国科学院生物物理研究所生物大分子国家重点实验室,北京100101 [2]中国科学院生物物理研究所北京百奥药业有限责任公司,北京100101

出　　处：《中国介入影像与治疗学》2004年第1期31-36,共6页Chinese Journal of Interventional Imaging and Therapy

摘　　要：临床上应用化疗药物治疗恶性肿瘤在许多情况下获得了一定的成功 ,但是 ,同时也存在着一些严重的问题。一个主要的问题是化疗药物普遍缺乏选择性 ,导致严重的剂量依赖性毒副作用的产生 ,极大地限制了化疗药物的临床治疗效果。为了降低化疗药物的非特异性毒性和提高对肿瘤的治疗效果 ,利用肿瘤细胞的表面总是过量表达一些蛋白质 ,这些蛋白质被称为“肿瘤标志物”可被作为选择性输送治疗性药物的“靶”。将细胞毒物质靶向输送到肿瘤标志物是一个早期的理想化的药物输送模式被称为“魔弹” ,这一假说的提出点燃了人们对肿瘤治疗的过高期望 ,但多年的研究结果是相当令人失望的。随着肿瘤靶向治疗机制的深入研究 ,人们获得了新的认识并对肿瘤的靶向治疗进行重新评价。一些正在临床前或临床研究中的具有药理活性的物质能够选择性地靶向和阻断生长因子等肿瘤标志物与它们受体的作用 ,如单克隆抗体 ,双特异性抗体 ,单克隆抗体与药物、毒素或放射性同位素的结合物 ,小肽和拟肽类分子以及他们与药物的结合物 ,反义寡核苷酸 ,包裹药物的免疫脂质体 ,小分子抑制剂等。本文重点介绍怎样用新的生物技术和方法来解决“魔弹”假说所遇到的一些问题。The clinical use of chemotherapeutic agents agai nst malignant tumors is successful in many cases but suffers from major drawbacks, o ne of which is lack of selectivity, leading to severe side effects and limited e fficacy. To limit non-specific toxicity and to improve the efficiency of cancer therapy, ”tumor markers”, which are proteins generally overexpressed on the s ur face of tumor cells, can be selectively targeted. The targeting of cytotoxic sub stances to tumor markers with ”magic bullets” is an old idea that raised high ex pectations but also disappointment. Over the past decade, newly gained understan ding of mechanisms for targeted therapy have brought new hopes. Pharmacological agents that selectively target tumors have been attempted, such as monoclonal an tibodies (mAbs) (whole molecule or fragments), bispecific antibodies, mAbs conju gated to drugs, toxins or radioisotopes, small peptidic and peptidomimetic molec ules in free form or conjugated to drugs, anti-sense oligonucleotides, immunoli posomes-encapsulated drugs, and small molecule inhibitors. This review will foc us on how new biotechnologies are helpful to resolve the challenges of the magic -bullet hypothesis and current developments of selective targeting in the manag ement of tumors.[

关 键 词：肿瘤 靶向介入 治疗 

分 类 号：R730.5[医药卫生—肿瘤]