医学
背景(考古学)
PARP抑制剂
乳腺癌
临床试验
癌症研究
聚ADP核糖聚合酶
内科学
药理学
癌症
肿瘤科
聚合酶
生物
酶
生物化学
古生物学
作者
Joaquín Mateo,Michael Ong,David S.P. Tan,Michael Gonzalez,Johann S. de Bono
标识
DOI:10.1038/nrclinonc.2013.177
摘要
Several drugs targeting poly(ADP-ribose) polymerase (PARP) enzymes are under development. Responses have been observed in patients with germline mutations in BRCA1 and BRCA2, with further data supporting antitumour activity of PARP inhibitors in sporadic ovarian cancer. Strategies to identify other predictive biomarkers remain under investigation. Iniparib was purported to be a PARP inhibitor that showed promising results in randomized phase II trials in patients with triple-negative breast cancer. Negative results from a phase III study in this disease setting, however, tempered enthusiasm for this agent. Recently, data from in vitro experiments suggest that iniparib is not only structurally distinct from other described PARP inhibitors, but is also a poor inhibitor of PARP activity. In this context, the negative iniparib phase III data might have erroneously promulgated the notion that PARP inhibition is not an effective therapeutic strategy. Here, we scrutinize the development of iniparib from preclinical studies to registration trials, and identify and discuss the pitfalls in the development of anticancer drugs to prevent future late-stage trial failures.
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