Discovering novel chemotherapeutic drugs for the third millennium

There is enormous potential for the discovery of innovative cancer drugs wi th improved efficacy and selectivity for the third millennium. In this revi ew we show how novel mechanism-based agents are being discovered by focusin g on the molecular targets and pathways that are causally involved in cance r formation, maintenance and progression. We also shaw how new technologies , from genomics through high throughput bioscience, combinatorial chemistry , rational drug design and molecular pharmacodynamic and imaging techniques , are accelerating the pace of cancer drug discovery. The process of contem porary small molecule drug discovery is described and progress and current issues are reviewed. New and potential targets and pathways for therapeutic intervention are illustrated. The first examples of a new generation of mo lecular therapeutics are now entering hypothesis-testing clinical trials an d showing activity. The early years of the new millennium will see a range of exciting new agents moving from bench to bedside and beginning to impact on the management and cure of cancer. (C) 1999 Published by Elsevier Scien ce Ltd. All rights reserved.