National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.
National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA; University of Arkansas at Little Rock, Little Rock, AR 72204, USA.
Trends Pharmacol Sci. 2017 Oct;38(10):852-872. doi: 10.1016/j.tips.2017.06.005. Epub 2017 Jul 11.
Tremendous efforts have been made to elucidate the basis of cancer biology with the aim of promoting anticancer drug development. Especially over the past 20 years, anticancer drug development has developed from conventional cytotoxic agents to target-based and immune-related therapies. Consequently, more than 200 anticancer drugs are available on the market. However, anticancer drug development still suffers high attrition during the later phases of clinical development and is considered to be a difficult and risky therapeutic category within the drug development arena. The disappointing performance of investigational anticancer candidates implies that there are some shortcomings in the translation of preclinical in vitro and in vivo models to humans, and that heterogeneity in the patient population presents a significant challenge. Here, we summarize both successful and failed experiences in anticancer development during the past 20 years and help identify why the current paradigm may be suboptimal. We also offer potential strategies for improvement.
人们付出了巨大努力来阐明癌症生物学的基础，旨在促进抗癌药物的开发。特别是在过去的 20 年中，抗癌药物的开发已经从传统的细胞毒性药物发展到了针对特定靶点和免疫相关的治疗方法。因此，市场上有 200 多种抗癌药物。然而，抗癌药物的开发在临床开发的后期阶段仍然存在高淘汰率，并且被认为是药物开发领域中一个困难和高风险的治疗类别。有前途的抗癌候选药物的表现令人失望，这意味着将临床前的体外和体内模型转化为人类的过程中存在一些缺陷，并且患者人群的异质性是一个重大挑战。在这里，我们总结了过去 20 年中抗癌药物开发的成功和失败经验，以帮助确定为什么当前的模式可能并不理想。我们还提供了潜在的改进策略。
