Protein biomarkers and drug design for cancer treatments

The development of new cancer treatments is quickly evolving away from traditional practices of the last 25 years. This change is occurring not only at the technical level, but also conceptually as the human genome is unravelled and decades of research contribute to our understanding of the molecular complexity of this disease. It is anticipated that disease initiation and progression is dictated by an understandable set of acquired capabilities. Knowledge of the molecular events associated with these acquired capabilities will allow the development of targeted agents coupled with new biomarkers for the prevention of cancer progression. This will have a profound influence on how drugs are developed, approved, and used by the medical community. The Food and Drug Administration (FDA) has over 400 Investigational New Drug (IND) applications for cancer in its portfolio, which increasingly involve molecular targets and genomic applications. However, only one-fifth of IND agents succeed in New Drug Application (NDA) and there is more expense and uncertainty around successful drug development than ever before. Biomarkers should help the success rate of INDs by enhancing the link between target and disease as well as in improving patient selection and monitoring response. In this review, we discuss how biomarkers can be used for target validation and pharmacodynamic modeling in preclinical drug discovery. We then explore the use of biomarkers in clinical development from proof of mechanism to proof of concept studies, as well as their use in the prevention setting.