Lessons Learned from Two Decades of Anticancer Drugs

被引:71
|
作者
Liu, Zhichao [1 ]
Delavan, Brian [1 ,2 ]
Roberts, Ruth [3 ,4 ]
Tong, Weida [1 ]
机构
[1] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA
[2] Univ Arkansas, Little Rock, AR 72204 USA
[3] ApconiX, BioHub & Alderley Pk, Alderley Edge SK10 4TG, Cheshire, England
[4] Univ Birmingham, Birmingham B15 2TT, W Midlands, England
关键词
CANCER STEM-CELLS; IN-VITRO; PRECISION MEDICINE; TUMOR XENOGRAFTS; MULTIDRUG-RESISTANCE; MYELOID-LEUKEMIA; ONCOLOGY DRUGS; CLINICAL-TRIAL; UNITED-STATES; MOUSE MODELS;
D O I
10.1016/j.tips.2017.06.005
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:852 / 872
页数:21
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