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A systems biology approach to oncology drug development
Published on August 31, 2015 32 min
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BIRGIT SCHOEBERL: Hello. My name is Birgit Schoeberl, and I work for Merrimack Pharmaceuticals. We are based in Cambridge, Massachusetts. The company is a biotech company based on systems biology. We are about 14 years old. And I'm happy to be here today to talk to you about the story of our anti-ErbB3 antibody MM-121 and use that as an example of how systems biology can be used in drug development.
So where has the state of oncology drug development been? In general, the focus has been on correlating how individual genes drive tumor growth, also called oncogenic drivers. And the single one-to-one correlation resulted in a series of very interesting targeted therapies, like Crizotinib to treat ALK mutations, Herceptin to treat tumors with Her2 amplifications. And they're, in general, very effective, but the problem with these types of therapies that are targeted at single mutations driving tumor growth, are that there's only very few patients that have tumors that are dependent on these mutations. So the prevalence ranges, in general, 10% to 15%. So why do we need to understand the networks and systems? Why do we need systems biology? Often there are no simple one-to-one correlations, and the tumors are dependent on multiple pathways, or the dependents are much more complex. And now, we are in the fortunate situation that most of the components of human cells are known, thanks to the Human Genome Project. So now it's really up to us to understand how these components play together in healthy as well as disease states. So we get to this holistic understanding of what is driving tumor growth, that will allow us to identify critical drivers of tumor growth, that are not necessarily mutated, but most likely, more abundant. And what I'd like to do today is show you an example of how we did that and identified ErbB3 as a target, and discovered 121 and anti-ErbB3 antibody, as well as predictive response biomarkers that were, later on, implemented in our clinical trials. So in the next slide, I will show you a schematic of how we use network biology, or systems biology, in practice.