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.

为了阐明抗癌药物的开发，已经做出了巨大的努力来阐明癌症生物学的基础。尤其是在过去的20年中，抗癌药物的开发已从传统的细胞毒剂发展成为基于靶标和免疫相关的疗法。因此，市场上可以买到200多种抗癌药。但是，在临床开发的后期阶段，抗癌药物的开发仍会遭受高消耗，并且被认为是药物开发领域中的一个困难而危险的治疗类别。研究性抗癌候选人令人失望的表现意味着有在临床前翻译一些缺点在体外和体内对人类而言，这种模型是巨大的挑战，而患者群体的异质性提出了重大挑战。在这里，我们总结了过去20年中在抗癌发展方面的成功和失败经验，并有助于确定为什么当前的范例可能不是最理想的。我们还提供了潜在的改进策略。