Contact:
Louise Grochow, MD, FACP
Chief, Investigational Drug Branch
CTEP/DCTD/NCI
Telephone: 301-496-1196
E-mail: grochowl@ctep.nci.nih.gov

Objective of Project:
The objective of this RFA is to create a series of multidisciplinary and translational research teams, each of which will focus on a critical biological process that is currently thought to contain high-priority targets for cancer drug discovery for the treatment of established cancers or the prevention of molecular changes that may cause cancer. For a particular target or class of targets, each team will advance the state of the pertinent science to facilitate the development of tools, probes, assays and imaging suitable for assessing in vivo in preclinical models and proof of principle clinical trials the effects of drugs on that target class.

Description of Project:
The discovery of molecular targets and their exploitation for the prevention and treatment of cancer presents difficult challenges: how are these targets to be validated, what does target based drug discovery imply for clinical trials methodology, what will suitable endpoints be and how will drug doses be identified? Clinical trials of these novel agents should focus on endpoints that assess the effect of an agent on its putative targets. To make such trials possible, target specific probes that accurately indicate drug effect on its target and are practical for use in the clinic must be developed. The need to assess target effects is made particularly urgent by new classes of agents that may produce effects that take a long time to become clinically apparent. Confirming that the hoped for biologic effect is achieved (or assessing reasons for failure to achieve it) will be critical in proof of principle preclinical and clinical trials to avoid the expense and futility of carrying ineffective agents into full- scale clinical development. The development of clinically useful probes for the molecular effects of agents will require outstanding multidisciplinary teams with broad expertise covering many areas of science and technology. Teams are not limited to a single institution and collaborating investigators may be recruited from academic, industrial or government institutions. These teams should attract outstanding basic scientists committed to target based drug discovery, clinical scientists vested in translating the basic science to clinical trials, experts in non- invasive (imaging) and invasive (tissue sampling) assessment of drug effects into active ongoing collaborations.