David A. Karnofsky Memorial Award Lecture

THE EXPANDING knowledge of signaling pathways regulating cell growth, cell cycle progression, and programmed cell death has led to a dramatic improvement in our understanding of the molecular events involved in cancer. This knowledge has allowed the identification of numerous targets for anticancer agents. As we move forward into an era of molecularly targeted therapeutics, it is worth reviewing some of the lessons learned from the development of one the prototype drugs of this class, imatinib (Gleevec, Glivec, formerly STI571; Novartis, Basel, Switzerland). However, it is also worth noting that the concept of specific targeting of cancer is certainly not new and in fact, was the basis for one of the drugs developed by Dr David Karnofsky, l-asparaginase. What differs is our ability to target specific pathways that are critical to the pathogenesis of cancer based on the knowledge gained over the past several decades.