Phenotypic screening in cancer drug discovery - past, present and future

A partir d'une étude des modes de développement de molécules ayant bénéficié d'une autorisation de mise sur le marché par la "Food and Drug Administration" entre 1999 et 2013, ces deux articles analysent les perspectives offertes par une approche dite de "criblage fonctionnel", par contraste avec une approche basée sur des cibles moléculaires identifiées, pour développer de nouveaux traitements anticancéreux

Résumé en anglais

There has been a resurgence of interest in the use of phenotypic screens in drug discovery as an alternative to target-focused approaches. Given that oncology is currently the most active therapeutic area, and also one in which target-focused approaches have been particularly prominent in the past two decades, we investigated the contribution of phenotypic assays to oncology drug discovery by analysing the origins of all new small-molecule cancer drugs approved by the US Food and Drug Administration (FDA) over the past 15 years and those currently in clinical development. Although the majority of these drugs originated from target-based discovery, we identified a significant number whose discovery depended on phenotypic screening approaches. We postulate that the contribution of phenotypic screening to cancer drug discovery has been hampered by a reliance on 'classical' nonspecific drug effects such as cytotoxicity and mitotic arrest, exacerbated by a paucity of mechanistically defined cellular models for therapeutically translatable cancer phenotypes. However, technical and biological advances that enable such mechanistically informed phenotypic models have the potential to empower phenotypic drug discovery in oncology.