Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Biruni University, Istanbul, Turkey.
Curr Med Chem. 2018;25(15):1704-1719. doi: 10.2174/0929867325666171129215610.
Many impediments of current anti-cancer therapies have urged scientists to discover new agents. As a result of growing spectrums of new targets and strategies and recent biological and biotechnological progresses, many anti-cancer agents such as monoclonal antibodies, small molecule tyrosine kinase inhibitors and epigenetic drugs have been reached to clinical trials.
This review helps to understand the rationale for the development of inhibitors against major targets such as cell growth, proliferation, survival, angiogenesis and recent targets such as proteasome, heat shock proteins, and epigenetics.
Recent approaches of the target-based anti-cancer drug developments were highlighted to giving some examples from approved agents. Many factors, such as metabolic change, hypoxia, cancer precursors and cancer resistant cells, and their effect on drug resistance mechanisms were discussed. The impacts of advanced computational techniques to identify targets of cancer and designing more selective inhibitors were explained.
Contributions of recent techniques such as a network analysis, the precise modes of action and computational methodologies especially simulation of bio-molecular processes to clarify targets, mechanism actions and reasons of lack of efficacy of anti-cancer drugs have been explained. The relationship between the several mechanisms and molecular design strategies has been discussed.
This review provides an overview of important targets and design strategies of anti-cancer drugs, advantages and disadvantages of these methods and evaluation of some currently used anticancer targets in clinical studies.
许多当前抗癌疗法的障碍促使科学家发现新的药物。由于新靶点和策略的范围不断扩大，以及最近的生物学和生物技术的进步，许多抗癌药物，如单克隆抗体、小分子酪氨酸激酶抑制剂和表观遗传学药物，已经进入临床试验。
本文综述有助于理解针对主要靶点（如细胞生长、增殖、存活、血管生成）和最近靶点（如蛋白酶体、热休克蛋白和表观遗传学）开发抑制剂的原理。
强调了基于靶点的抗癌药物开发的最新方法，并从已批准的药物中举例说明。讨论了许多因素，如代谢变化、缺氧、癌症前体和耐药细胞，以及它们对耐药机制的影响。解释了先进计算技术在识别癌症靶点和设计更具选择性抑制剂方面的作用。
本文解释了网络分析、精确作用模式和计算方法等最新技术的贡献，特别是生物分子过程模拟，以阐明靶点、作用机制和抗癌药物疗效不佳的原因。讨论了几种机制与分子设计策略之间的关系。
本文概述了抗癌药物的重要靶点和设计策略、这些方法的优缺点，以及目前在临床研究中使用的一些抗癌靶点的评价。
