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Feb 15, 2009 (Vol. 29, No. 4)

Pathway Knowledge Can Benefit Cancer Therapeutics

Analytical Methodologies Show Promise in Identifying Points for Intervention

  • Personalized Medicine

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    XB-BioIntegration Suite (XB-BIS) was developed at the Van Andel Research Institute to support multidisciplinary translational research.

    At the Van Andel Research Institute, Craig Webb, Ph.D., director of the program of translational medicine, and his team are building a roadmap to personalized medicine based on a multidisciplinary approach that includes research laboratory, informatics, and outcomes in the clinic. 

    Since joining the Van Andel Institute, Dr. Webb has been building on the wealth of knowledge from genomics and biomarkers to develop a practical approach to optimal therapeutic selection for individualized molecular-based medicine for oncology patients.   

    Specifically, in his presentation at the “Tri-Conference,” Dr. Webb will outline his team’s ongoing efforts to utilize molecular information derived from individual patient tumors in conjunction with knowledge of biomarker-drug interaction to predict treatments for an improved therapeutic index. Using network theory and mathematical modeling to develop a signature-based targeted-expression pattern, Dr. Webb and his colleagues are working to understand why some therapies work or others don’t for patients in the current clinical trial studies the team is involved in.  Results from their clinical experiences are rolled into their ongoing preclinical research effort that is focused on understanding the underlying mechanisms involved in the developing cancer state.

    “We have developed a software application suite, XB-BioIntegration Suite (XB-BIS), to support our multidisciplinary translational research. The application serves as a common interface for the consolidation of the clinical, preclinical, and molecular data, and a variety of analytical, visualization and reporting tools,” Dr. Webb reports. “The software allows for bidirectional flow of real-time data and information between multiple clinical and research components of the project. This portal provides our internal team and our clinical collaborators with a forum to share data and visualize analytical outcomes.”

  • Multidimensional Pathways in Cancer

    Michael Leibman, Ph.D., president and managing director of Strategic Medicine, outlined what his company is focused on.

    Strategic Medicine, a team of six principals, was founded to ask some hard questions, including the question of whether or not the medical community is practicing medicine optimally. Partnering with consultants, as well as basic and clinical medical researchers, Dr. Leibman and his team are taking a look at the bigger picture to determine whether we’re ready for personalized medicine. Given the complexities of how diseases present in the clinic and the observation that patients rarely present with a single disease, do we know enough about disease pathways to diagnose and practice medicine optimally? 

    “Disease is a process, not a chronic state. We continually observe dynamic changes in a patient with disease and in response to the therapeutic regime they’re given. These changes impact the presentation of the disease throughout the course of the therapy,” Dr. Leibman explains. “The ways in which we describe the process impacts our ability to stratify our patients and provide them with the most efficacious therapy available.

    “We are currently looking at approximately 800 variables in an attempt to extract the most critical ones that tie back to the underlying biology of the disease state. There is a richness of qualitative data that exists, and we’re working toward making that data more quantifiable.”

    Dr. Leibman and his team are building their models on the knowledge base that exists for breast cancer. In breast cancer, there is a wealth of knowledge at the molecular level and extensive clinical experience that exists for the disease. But to fully understand the breast cancer disease state, Dr. Leibman reports that they need to develop network models that look beyond a single-dimensional view and incorporate all forms of molecular data from gene-expression levels to protein networks to metabolic data from actual patients. The analysis then takes a look at the gaps in understanding to determine what’s left out in the model. 

    Strategic Medicine works on a global basis to monitor the impact of drugs on patients around the world. It is also working with pharmaceutical firms to change how they approach drug discovery. It hopes to balance the biological screening process with the economics involved to determine how best to integrate new drug candidates into the standard practice used by physicians today. By way of example, understanding off-target risks of drug candidates that can be anticipated and eliminated early in the drug discovery process is key to avoiding failures in clinical trials, or worse, post-market release.

    The Strategic Medicine approach is really disease agnostic—the current modeling being done with breast cancer will be extrapolated to other disease states. While it is continuing to make inroads toward stratified medicine, Strategic Medicine indicated that the medical community is not yet ready to deliver personalized medicine.

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