Abstract KN01: Overcoming barriers to new drug development.

Abstract

Abstract The forty years that followed the signing of the National Cancer Act witnessed substantial progress in our understanding of the biology of human cancer. This knowledge has translated into several important advances for the treatment of patients with both hematological and solid tumor malignancies. Yet, during the last 15 years we have not seen a proportional increase in the approval rate of new drugs. The drop-off in efficiency of drug development coincided, unexpectedly, with the adoption of target-based screening, which replaced a physiological or phenotypic approach. The power of molecular biology enticed drug developers to believe that the ability to express a cloned gene product to high purity and the utility of structural biological approaches to rational drug design, led to remarkably potent and selective inhibitors. Unfortunately, the understanding of how the target was wired into a specific tumor type was less obvious, making even optimal target engagement in the clinic insufficient to produce striking benefits to patients. The phenotypic approach is agnostic to target but instead relies on a readout that predicts efficacy in the clinic. For both the target-based and for the phenotypic approaches, the rate limiting step in cancer drug discovery is a predictive pre-clinical model of a specific tumor type. The challenges that remain and the advances we have made in translational research is the subject of this presentation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr KN01.