Conventional drug discovery strategies are typically 'target centric' based on the selection of lead compounds with optimised 'on-target' potency and selectivity profiles. However, high-attrition rates are often the result of compensatory or redundant cancer mechanisms and the fact that tumours do not find it difficult to escape inhibition of a single pathway. In this article, we highlight two emerging and complimentary technologies; namely phenotypic imaging and post-translational pathway profiling, which when combined with relevant disease models can provide pharmacodiagnostic and drug combination strategies that predict and counteract inherent and adaptive drug resistance. The implementation of such approaches at early stages of the drug discovery process enables more informed decisions on candidate drug selection and how to maximise and predict efficacy before clinical development.

中文翻译：

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结合成像和路径分析：癌症药物发现的另一种方法。

常规药物发现策略通常基于对前导化合物的选择，以具有最佳“针对性”的效能和选择性特征的“目标为中心”。然而，高流失率通常是代偿性或冗余性癌症机制的结果，并且肿瘤并不难以摆脱单一途径的抑制这一事实。在本文中，我们重点介绍了两种新兴的互补技术。即表型成像和翻译后途径分析，当与相关疾病模型结合使用时，可以提供能够预测和抵消固有耐药性和适应性耐药性的药物诊断和药物联合策略。