Molecular targets and cancer therapeutics: discovery, development and clinical validation

The AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held in Washington, DC on 16-19 November 1999 provided a forum for cancer research clearly showing evolution of a target and mechanism-driven science. The notion of the tumor as a tissue composed of heterogeneous populations of normal and abnormal cells as viable targets is coming to the fore with the advent of agents directed toward non-malignant cell targets. Growth control rather than eradication as a treatment strategy for malignant disease is being tested preclinically and clinically. Among targets, kinases are in the lead with nuclear, cytoplasmic and membrane kinases being selectively inhibited by small molecules and macromolecules. First generation tumor vasculature-directed agents are progressing through early clinical studies. The interest in tumor vasculature as a target has renewed interest in imaging technology to discern biological effect and in tumor hypoxia. This has resulted in elucidation of molecular responses triggered by a low oxygen environment. Challenges remain in the areas of cellular and immune therapies. Dendritic cell-based vaccines are being tested preclinically in many systems. Interleukin-12 is proceeding through clinical trials. Apoptosis-protective molecules such as bcl-2, and apoptosis-stimulating molecules such as bar, are being pursued as targets for inhibition and activation, respectively. Finally, methods and technology to aid in the identification of new targets were highlighted. This perspective, while it is by no means an exhaustive review of the presentations, brings forward some of the main topics and interests that are current in cancer research. Targets were the topic but methods of target identification and the need for increased chemical diversity to selectively focus agents to targets with small differences were also major topics of discussion. (C) 2000 Harcourt Publishers Ltd.