药物靶标的鉴定和作用机制的生化研究是现代药物开发的主要问题。本文是对经典的“一种药物”“一个靶点”范式的批判性回顾。事实上，基于蛋白质质谱的靶解卷积和耐药菌株研究的新方法表明，病原体对外源性物质的反应涉及多种基因产物和适应机制，而不是单一基因或基因产物。对药物的耐药性可能与蛋白质结合研究中与药物相互作用以外的其他蛋白质的差异表达有关，并导致复杂的细胞生理适应。因此，阐明作用机制需要蛋白质组学以外的方法。本综述的重点是原生动物病原体。然而，这些结论可以扩展到针对其他病原体或癌症的化疗。

Identification of drug targets and biochemical investigations on mechanisms of action are major issues in modern drug development. The present article is a critical review of the classical "one drug"-"one target" paradigm. In fact, novel methods for target deconvolution and for investigation of resistant strains based on protein mass spectrometry have shown that multiple gene products and adaptation mechanisms are involved in the responses of pathogens to xenobiotics rather than one single gene or gene product. Resistance to drugs may be linked to differential expression of other proteins than those interacting with the drug in protein binding studies and result in complex cell physiological adaptation. Consequently, the unraveling of mechanisms of action needs approaches beyond proteomics. This review is focused on protozoan pathogens. The conclusions can, however, be extended to chemotherapies against other pathogens or cancer.