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| Zentam Tsuchihashi, Bristol-MyersSquibb |
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Dr. Zenta Tsuchihashi works on the oncology biomarker research program at Bristol-Myers Squibb. After receiving his Ph.D. in pharmaceutical sciences from the University of Tokyo, he moved to the US for a postdoctoral training in Dr. Arthur Kornberg’s and Dr. Patrick Brown’s laboratories at Stanford University. There, he studied the bacterial DNA replication enzymes, the mechanism of translational frameshifting, and the actions of HIV nucleocapcid protein. Before joining Bristol-Myers Squibb in 1999, he worked in the areas of gene therapy vector development at Somatix Therapy and genetic disease gene discovery at Mercator Genetics. He was a key member of the Mercator team that identified the hereditary hemochromatosis gene in 1996. At Bristol-Myers Squibb his team has been working on genomic biomarker analysis in various therapeutic areas. His current focus is the discovery of predictive and pharmacodynamic biomarkers for oncology drugs especially in the immunotherapy area. He also is a member of the genomics technical group at PhRMA. He has authored and co-authored over twenty peer reviewed articles.
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Many layers of biomarker roles in tumor immunotherapy
Zenta Tsuchihashi, Bristol-Myers Squibb
Based on the “Critical Path” document that appeared in 2004, FDA recently released two follow up documents, “Critical Path Opportunities List” and “Critical Path Opportunities Report”. In these documents, FDA identified the development of new biomarkers as one of the key opportunities to increase efficiency, predictability, and productivity in drug development. In parallel, there is a recognition on the industry side that the identification of novel biomarkers and the actual utilization of them needs to be a key ingredient of the drug development. I will discuss the key considerations in the study of clinical biomarkers especially for the development of anti-cancer immunotherapy. For the treatment to be effective, enough quantity of the drug has to be present at the site of the action for enough time (pharmacokinetics), and then that needs to generate a sufficient amount of action (pharmacodynamics). And the latter, the pharmacodynamic process itself consists of multiple steps. First, there is a binding of the drug to the target, followed by a stimulation of the immune system. This leads to an anti-tumor attack by the host immune system, then ultimately there should be a destruction of the tumor cells. Different biomarkers can potentially monitor each of these steps, and they give us a more precise picture of how the drug is acting, complementing the clinical observations. This additional information from biomarker analyses provides us a critical tool for the key decisions in the development of this drug. However, despite the technological advances especially in the genomics area that can now create a flood of biomarker candidates, developing and ‘qualifying’ these candidate markers to generate a utility is still not a straightforward process, and it requires a careful thinking and well-planned clinical studies.
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