Robert J
Institut Bergonié, Bordeaux, France.
Bull Cancer. 1996 Oct;83(10):801-8.
In vitro models have been intensively developed for several years for selecting new anticancer agents. The National Cancer Institute has even chosen as a primary screen of new molecules a panel of 60 human tumor cell lines. However, it may seem hazardous to rely too much on in vitro models for the discovery and selection of new anticancer drugs: (1 because no metabolism of the compounds occurs in cell culture; (2 because an in vitro cell line cannot be representative of an in situ tumor cell population; (3 because antiproliferative activity is only part of antitumor activity; (4 because the toxicologic properties of the molecules are not taken into account by in vitro systems; (5 because cell cultures do not allow any selectivity study between tumor cells and normal cells. With examples drawn from three different therapeutic classes, anthracyclines, taxoids and camptothecin derivatives, we show that in vitro tests are insufficiently predictive of antitumor potential. The excess of confidence allowed to these models may lead to premature decisions which are not after that justified by clinical trials.
体外模型已被深入开发数年，用于筛选新型抗癌药物。美国国立癌症研究所甚至选用了一组60种人类肿瘤细胞系作为新分子的初步筛选模型。然而，过于依赖体外模型来发现和筛选新型抗癌药物可能存在风险：（1）因为化合物在细胞培养中不会发生代谢；（2）因为体外细胞系不能代表原位肿瘤细胞群体；（3）因为抗增殖活性只是抗肿瘤活性的一部分；（4）因为体外系统未考虑分子的毒理学特性；（5）因为细胞培养不允许对肿瘤细胞和正常细胞之间进行任何选择性研究。通过从蒽环类、紫杉烷类和喜树碱衍生物这三种不同治疗类别中选取实例，我们表明体外试验对抗肿瘤潜力的预测不足。对这些模型过度信任可能导致过早做出决策，而这些决策之后并不能由临床试验来证明其合理性。
