BETHESDA, MarylandThe 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
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
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