Before molecular pathways in cancer were known to a depth that could predict targets, drug development relied on phenotypic screening, where the effectiveness of candidate chemicals is judged from functional readouts without considering the mechanisms of action. The unraveling of tumor-specific pathways has brought targets for molecularly driven drug discovery, but precedents in the field have shown that awareness of pathways does not necessarily predict therapeutic efficacy, and many cancers still lack druggable targets. Phenotypic screening therefore retains a niche in drug development where a targeted approach is not informative. We analyze the unique advantages of phenotypic screens, and how technological advances have improved their discovery power. Notable advances include the use of larger biological panels and refined protocols that address the disease-relevance and increase data content with imaging and omic approaches.

在深入了解癌症中的分子途径并可以预测靶标之前，药物开发依赖于表型筛选，其中候选化学物质的有效性是根据功能读数来判断的，而不考虑作用机制。肿瘤特异性途径的阐明为分子驱动的药物发现带来了靶点，但该领域的先例表明，对途径的认识并不一定能预测治疗效果，而且许多癌症仍然缺乏可成药的靶点。因此，表型筛选在药物开发中保留了一个利基市场，其中靶向方法无法提供信息。我们分析表型筛选的独特优势，以及技术进步如何提高其发现能力。显着的进步包括使用更大的生物面板和完善的协议来解决疾病相关性并通过成像和组学方法增加数据内容。