BETHESDA, Maryland—The understanding of carcinogenesis that has emerged from molecular and genetic studies has provided a new vision of treatment, commonly called molecular targeting. In it, debilitating cytotoxic drugs will give way to agents that target specific proteins that mark specific cancer cells.
In recent years, the National Cancer Institute has focused its drug development efforts on defining targets and agents to attack these targets. Some targeted drugs would cause tumors to shrink and disappear. Others would block tumor growth and stabilize tumor size.
The previous article in this series described NCI’s cancer signature program. In this interview, Edward A. Sausville, MD, PhD, of the Division of Cancer Treatment and Diagnosis, discusses the Institute’s related program in molecular target research with Patrick Young, ONI’s Washington bureau chief.
ONI: How do molecular targets of prevention and treatment differ from the signatures of cancer cells?
Dr. Sausville: There could be some overlap. A signature defines molecules that are differently expressed in different tumors and in comparison to normal tissues. These molecules may then actually be targets in their own right and, thus, the basis for starting a drug discovery campaign. It is also possible that some signatures might be suitable in a diagnostic sense but not really have a role in treatment or prevention. The key point is that we are going to get information from the signatures program, which then becomes useful for drug discovery.
ONI: What are the advantages of selectively attacking molecular targets?
Dr. Sausville: The hoped-for outcomes are therapeutic agents that seek out specific targets, are fairly well tolerated, and have a wide range between their efficacious concentrations and their toxic concentrations. Unfortunately, the agents that we have at the moment in the therapeutic armamentarium for cancer have a fairly close relationship between active and toxic concentrations.
