Boven E, Winograd B, Fodstad O, Lobbezoo M W, Pinedo H M
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
Eur J Cancer Clin Oncol. 1988 Mar;24(3):567-73. doi: 10.1016/s0277-5379(98)90039-6.
In an attempt to increase the predictability and to extend the differential capacity of the anticancer drug development program the American National Cancer Institute has recently proposed the introduction of a screening system consisting of human tumor cell lines to select drugs in a disease-oriented fashion rather than by the previously applied drug-oriented strategy. Although this new approach offers great advantages, assay limitations can be identified in testing unknown compounds for antitumor activity in vitro. Human tumor xenografts grown in nude mice may play an additional role in the prediction of clinical activity and the assessment of the spectrum of activity of potential anticancer drugs, because they have a better relationship with the clinical situation of cancer treatment. In a European multicenter collaboration it has been proposed to use panels of human tumor lines from solid tumor types to study: the antitumor activity of three different drugs per tumor type; the reliability of 'preclinical' phase II studies by comparison of the obtained data with results of phase II clinical trials; the feasibility of this joint project, such as the methodology, the reproducibility of experimental data and the introduction of uniform activity criteria. If preclinical phase II studies in human tumor lines generate reliable results, this in vivo screening system will create a unique possibility to better identify promising clinical candidate compounds or analogs of conventional cytostatic agents as well as those tumor types likely to respond to the selected investigational drugs.
为提高抗癌药物研发计划的可预测性并扩大其鉴别能力，美国国立癌症研究所最近提议引入一种由人类肿瘤细胞系组成的筛选系统，以便以疾病导向的方式而非先前采用的药物导向策略来筛选药物。尽管这种新方法具有诸多优势，但在体外测试未知化合物的抗肿瘤活性时，仍可发现检测方法存在局限性。在裸鼠体内生长的人类肿瘤异种移植瘤可能在预测临床活性以及评估潜在抗癌药物的活性谱方面发挥额外作用，因为它们与癌症治疗的临床情况有更好的相关性。在一项欧洲多中心合作中，有人提议使用来自实体瘤类型的人类肿瘤细胞系面板来研究：每种肿瘤类型中三种不同药物的抗肿瘤活性；通过将所得数据与II期临床试验结果进行比较，评估“临床前”II期研究的可靠性；该联合项目的可行性，如方法学、实验数据的可重复性以及统一活性标准的引入。如果在人类肿瘤细胞系中进行的临床前II期研究能产生可靠结果，那么这种体内筛选系统将为更好地识别有前景的临床候选化合物或传统细胞抑制剂的类似物，以及可能对所选研究药物有反应的肿瘤类型创造独特的机会。
