Identifying and prosecuting the right targets in oncology


Year:

Session type:

Graeme Smith1
1AstraZeneca, Alderly Park, UK

Abstract

Over the last decade or so efforts in oncology drug discovery have shifted form a target based approach to one that is much more patient aligned. Whilst the former approach produced robust pipelines of potential targets, these often lacked strong disease linkage. Patient aligned drug discovery embeds the molecular definition of the cancer that the project aims to treat at the heart of the discovery cascade. The outputs of this transformation are that targets are selected with a clear line of sight to a defined and identifiable population in the clinic. This should ultimately allow earlier clinical decisions to be made and in a more cost-effective manner.  

In defining the required attributes of a cancer target evidence must exist that a target contributes to the development or progression of the cancerous phenotype. Disease linkage can be identified by mutation, amplification or aberrant activation. Patient selection feasibility also needs to be considered along with how novel targets are linked to clinically defined populations and whether there is a clinically amenable biomarker. As has been classically performed in oncology drug discovery, feasibility of screens for novel oncology targets needs to be assessed along with the druggability of the identified target.  Challenges still remain in the target identification and validation space with a greater understanding of novel targets needed in the context of a disease which exhibits intra and inter-patient heterogeneity and pathway redundancies. As well as discussing the concepts outlined above, specific examples of targets with a clear line of sight to clinical segments that we have been working on will be presented, along with more practical considerations.