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Profiling an Oncology Drug with In Vitro Assays and In Vivo Models to Better Understand its Potential Clinical Applications



December 14, 2017
1 pm to 2 pm EST

 

Sponsored by
Eurofins Pharma Discovery Services Logo

Preview:

 

Webinar Description:

A case study will be presented that illustrates how careful profiling of an oncology drug can yield valuable information in the drug discovery and development stage to help guide candidate selection. Sorafenib was initially developed as an inhibitor of the Raf serine/threonine protein kinases and selected for clinical evaluation in melanoma patients. However, sorafenib demonstrates a relatively broad spectrum of kinase inhibition, including several receptor tyrosine kinases that are important for the process of angiogenesis. While sorafenib showed disappointing results in melanoma clinical trials, it proved to be an excellent drug in trials directed towards heavily vascularized tumors, and has subsequently been approved for the treatment of hepatocellular and renal carcinomas, as Nexavar®.

To help illustrate why sorafenib has the clinical utility that it does, profiling data in complementary assays will be discussed. This includes evaluation in an in vivo syngeneic model with data from our partner lab Pharmacology Discovery Services. Examples with in vitro assays will start with evaluation of this drug’s kinase inhibition spectrum, using the KinaseProfiler™ platform, followed by phenotypic profiling against a broad and diverse range of human tumor cell lines using the OncoPanel™ Cell-Based Profiling Service. Comparing this profile of sorafenib with that of another Raf inhibitor, vemurafenib, will show how the two inhibitors have different profiles, which helps to explain their different clinical utilities. An example on how phenotypic data can be used to identify predictive genomic biomarkers for sensitivity and resistance will further demonstrate the clinical application of sorafenib. In summary, the careful evaluation of a potential oncology drug in appropriate in vitro and in vivo systems can yield useful information to help guide clinical trials, or allow repurposing of an existing drug candidate asset.

Learning Objectives:

  • Learn how the collective use of data from profiling an oncology drug candidate can be valuable in demonstrating potential clinical utility – using a case study with sorafenib
  • Translate observed pre-clinical in vitro and in vivo data to gain increased insight during candidate selection
  • Empower decision making by using in vitro profiling data to identify predictive biomarkers of sensitivity and resistance

Speaker:

Dr. Alastair King, PhD

OncoPanel™ Cell-Based Assays Group Leader

Eurofins Pharma Discovery Services

Dr. King has over 17 years of research experience, with a focus on oncology drug discovery, cellular assays, and laboratory automation. After completing his post-doctoral studies in the areas of vision biochemistry and mitogenic pathway signaling, he has held positions of increasing responsibility at SmithKline Beecham, GlaxoSmithKline, Johnson & Johnson, and Eurofins Pharma Discovery Services, where he is currently group leader of the OncoPanel™ Cell-Based Profiling Service. He has significant experience in assay development across a variety of target types and therapeutic areas, using a broad range of formats for low to high-throughput applications. Dr. King has led international strategic initiatives and drug discovery teams, including that which discovered dabrafenib (Tafinlar®) for the treatment of metastatic melanoma. Since his undergraduate studies, where he worked on kinases that regulate protein translation, one of his major interests has been the area of protein phosphorylation and the prosecution of targets within that space for drug discovery. Dr. King holds a Ph.D. in Biochemistry from the University of Southampton and a B.Sc. in Biochemistry from the University of Bristol. He is also a member of the American Association for Cancer Research, and has received numerous awards for his work.



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