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Cancer researchers seek to predict tumor growth

Case Western Reserve University : 27 January, 2007  (Technical Article)
University Hospitals of Cleveland and the Case Western Reserve University schools of medicine and engineering have launched a revolutionary investigation in cancer research as part of a National Cancer Institute effort that challenges engineers and oncologists with the development of a systems biology approach to gain understanding and to unlock issues of the most complex cancer biology problems.
“Our objective is to develop a fully integrated team of technology systems scientists and cancer biologists that will target an area of increasing significance called ‘mismatch repair defective malignancies’,” says Timothy J. Kinsella, M.D., the study’s principal investigator in Cleveland, Professor and Vincent K. Smith Chair of Radiation Oncology at the Case School of Medicine and University Hospitals of Cleveland. “These malignant cells cause various cancers, so we are investigating two basic approaches for destroying these MMR defective cells.”

This UHC/Case study, entitled “Complex Systems and Control of Mismatch Repair Deficient Cells,” is part of a new nine-site, $14.9 million NCI project called the Integrative Cancer Biology Program. Each site will focus on different targets with one overarching mission: to gain valuable information about the progression of cancer through a systems-wide approach. A multi-disciplinary effort among all fields of cancer research will incorporate genomics, proteomics, and molecular imaging using system theoretic techniques to develop new models that can be used in-silico, that is, in or by means of computer simulation to better understand and predict the dynamics of the cancer process.

MMR defective cells cause hereditary nonpolyposis colon cancer, an inherited disorder, also called Lynch syndrome, that often leads to colon cancer and other types of cancer, most often in people in the 20 to 40-year age group. The disorder affects about 160,000 people in the United States, most of them in their 20s and 30s. “These patients are resistant to current drugs on the market,” Dr. Kinsella says. “We need to find out why and how these cellular repair processes go awry.”

“Because the problem being studied involves biological processes that evolve at various levels (molecular, cellular, tissue, organ), and the individual dynamical processes interact at multiple spatial and temporal scales, this provides a unique and challenging opportunity for the application of systems and control methodologies,” says Kenneth A. Loparo, Ph.D., a co-principal investigator of the study and a professor in electrical engineering and computer science at the Case School of Engineering, “We are developing new modeling and analysis approaches based on a systems concept, and this work should provide new insight into the complex processes involved in the dynamics of cancer.”

The ICBP initiative highlights nine integrative biology centers. These centers will provide the nucleus for the design and validation of computational and mathematical cancer models. The models will simulate complex cancer processes, and will be used to address all stages of cancer, from the basic cellular processes through tumor growth and metastasis. “The key aspect that sets the ICBP effort apart from others,” said Daniel Gallahan, Ph.D., Associate Director, Division of Cancer Biology, NCI, “is the focus on building predictive cancer models, and not just analyzing data.”

The ICBP centers also will serve as training and outreach programs, enabling developing technologies to be communicated to other scientists in the cancer research community. This outreach effort adds another level of integration, and also provides the means for other scientists to validate the usefulness of these models.

The new ICBP centers represent a broad spectrum of cancer research. The centers and their individual projects include Massachusetts General Hospital, Boston, “Development of Virtual Tumor;” Dana Farber Cancer Institute, Boston, “Signatures of Kinase Activation in Cancer;” Lawrence Berkeley National Laboratory, Berkeley, Calif., “Systems-Based Predictions of Response to Cancer Therapy;” Ohio State University, “Interrogating Epigenetic Changes in Cancer Genomes;” Massachusetts Institute of Technology, Boston, “Regulatory Networks in Cancer Initiation and Progression;” Duke University, Durham, N.C., “Integration of Oncogenic Networks in Cancer Phenotypes;” Stanford University School of Medicine, Stanford, Calif.,“Computational Modeling of Cancer Biology;” Vanderbilt University Medical Center, Nashville, Tenn., “Multiscale Mathematical Modeling of Cancer Invasion.”

The ICBP centers also will interact and collaborate with other NCI programs and external groups. NCI’s Cancer Biomedical Information Grid program will coordinate all the bioinformatics software needed by the ICBP, part of caBIG’s ongoing effort to simplify and integrate the sharing and usage of data by providing access to NCI’s cancer research communities.
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