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February 24, 2004 • Volume 1 / Number 8 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Special ReportSpecial Report

Integrative Cancer Biology Program: Tackling Cancer's Complexity

In mid-January, a fierce snowstorm crippled much of the greater Washington, D.C. area - closing schools and businesses and forcing the federal government and most county governments to advise their employees to stay home. Nevertheless, more than 70 investigators from across the United States managed to find their way to NCI for an informational meeting about its new Integrative Cancer Biology Program (ICBP) and the opportunities for research that it may present.

"The interest in this program bodes well for its future," says Dr. Dinah Singer, director of the NCI Division of Cancer Biology. The goal of the ICBP is to promote the analysis of cancer as a complex biological system. Building on the expanding cache of knowledge about cells' "parts," or their constituent components, explains Dr. Singer, initiatives launched through ICBP will focus on concepts and methods that target the "whole" - biological systems and their integrated behavior. Doing so will require an increasing interdependence among cancer biologists, scientists from other fields that consider complex systems, and scientists with expertise in computational biology, because the success of integrative biology will rely heavily on developing robust computer models of biological systems.

"One of the major aims of the ICBP," Dr. Singer says, "is to facilitate the emergence of integrative cancer biology as a distinct field, with the ultimate goal of developing predictive computational models of various cancer processes that can be applied to the development of cancer interventions.

"We now appreciate that cancer is a disease of genes and we understand the regulation and function of a huge number of these genes and their protein products," she continues. "In many cases, we have a detailed understanding of how proteins interact, both structurally and functionally in regulatory, signaling, and metabolic pathways. What we are lacking is a systematic approach to integrate various kinds of data and processes into a comprehensive model where we can analyze the complex biological systems that are cancer."

Modeling Complexity
Integrative cancer biology is a subset of another burgeoning field, systems biology. Both are addressing questions of complexity - honing in on the structural and functional relationships among components of biological processes and attempting to quantify their interactions and measure how they change over time in response to various stimuli, such as environmental or genetic influences.

"The recognition that cancer is a complex disease is not a new one," says Dr. Dan Gallahan, associate director and chief of the division's Structural Biology and Molecular Applications Branch (SBMAB). "But until now, our ability to analyze this complexity has been limited both by the availability of large-scale data sets and appropriate mathematical approaches for manipulating the data." But over the past few years, things have changed. Large-scale data sets are now available, and the mathematics exists to construct multivariate, scalable models of complex systems that are dynamic and predictive.

"The challenge is to derive knowledge and understanding from them," Dr. Gallahan stresses. Computer-based modeling is used in areas such as mechanical and electrical engineering to design and test a variety of complex systems, such as printed microcircuits, jet planes, and cars. The advances in mathematics, engineering, and technology make it possible to begin developing simulations of cells and organs in individuals with and without cancer. The vision for the future, he says, is the development of individualized computer models that will help to predict, prevent, and treat cancers.

Collaboration a Must
Collaboration among a broad array of scientists clearly is vital to the success of the ICBP. "Through ICBP, research programs will be established that bring together cancer biologists and scientists from fields such as mathematics, physics, information technology, imaging sciences, and computer science to work on a common cancer biology program," says Dr. Jennifer Couch, SBMAB program director. "These programs will tackle a diverse array of issues, from gene expression to metabolic and signaling networks to more temporal processes like cancer initiation, progression, and metastasis."

Through the ICBP initiative, large, NCI-funded, multi-investigator teams will address questions of cancer complexity with a wide scope of research activities, Dr. Couch explains. These programs will go beyond research, though. They also will be responsible for establishing training and outreach programs that will further develop the field by actively disseminating new findings about cancer complexity and educating future investigators in the necessary approaches and skills. Although the programs will operate independently, they will be linked through a central focus on cancer, a common bioinformatics infrastructure, and an NCI-sponsored coordinating committee.

"We hope to create a community of interactive and collaborative cancer biology researchers that extends beyond the scope of the funded programs," Dr. Couch says. "A key aspect of the program will be the accessibility of the data and models to the larger research community."

The success of the January meeting, Dr. Singer says, clearly indicates that there is a sincere and eager interest in ICBP and systems biology in the research community.

"The emergence of integrative cancer biology as a field will be instrumental in fostering the growth of predictive and preventive medicine," she says. "As we continue to expand our knowledge about basic and clinical cancer biological processes, the area of integrative cancer biology will serve to synthesize this information into a comprehensive picture of cancer, paving the way for rational approaches to dealing with this disease."

For further information, please see RFA CA-04-013, Integrative Cancer Biology Program and the ICBP online.