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[抗癌治疗的个体化;肿瘤学新药的分子靶点]

[Individualization of anticancer therapy; molecular targets of novel drugs in oncology].

作者信息

Regulska Katarzyna, Stanisz Beata, Regulski Miłosz

机构信息

Wielkopolskie Centrum Onkologii im. Marii Curie-Skłodowskiej w Poznaniu, ul. Garbary 15, 61-866 Poznań, Poland.

出版信息

Postepy Hig Med Dosw (Online). 2012 Nov 15;66:855-67. doi: 10.5604/17322693.1019649.

Abstract

Deregulation of cellular signal transduction, caused by gene mutations, has been recognized as a basic factor of cancer initiation, promotion and progression. Thus, the ability to control the activity of overstimulated signal molecules by the use of appropriate inhibitors became the idea of targeted cancer therapy, which has provided an effective tool to normalize the molecular disorders in malignant cells and to treat certain types of cancer. The molecularly targeted drugs are divided into two major pharmaceutical classes: monoclonal antibodies and small-molecule kinase inhibitors. This review presents a summary of their characteristics, analyzing their chemical structures, specified molecular targets, mechanisms of action and indications for use. Also the molecules subjected to preclinical trials or phase I, II and III clinical trials evaluating their efficiency and safety are presented. Moreover, the article discusses further perspectives for development of targeted therapies focusing on three major directions: systematic searching and discovery of new targets that are oncogenic drivers, improving the pharmacological properties of currently known drugs, and developing strategies to overcome drug resistance. Finally, the role of proper pharmacodiagnostics as a key to rational anticancer therapy has been emphasized since the verification of reliable predictive biomarkers is a basis of individualized medicine in oncology.

摘要

由基因突变引起的细胞信号转导失调已被公认为是癌症起始、促进和进展的一个基本因素。因此,利用合适的抑制剂来控制过度激活的信号分子活性的能力成为了靶向癌症治疗的理念,这为使恶性细胞中的分子紊乱正常化以及治疗某些类型的癌症提供了一种有效工具。分子靶向药物主要分为两大类:单克隆抗体和小分子激酶抑制剂。本综述总结了它们的特性,分析了它们的化学结构、特定分子靶点、作用机制和使用适应症。还介绍了正在进行临床前试验或I、II、III期临床试验以评估其有效性和安全性的分子。此外,本文讨论了靶向治疗发展的进一步前景,重点关注三个主要方向:系统地寻找和发现作为致癌驱动因素的新靶点、改善现有药物的药理学特性以及制定克服耐药性的策略。最后,由于可靠的预测生物标志物的验证是肿瘤学个体化医学的基础,因此强调了适当的药物诊断作为合理抗癌治疗关键的作用。

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