2010 San Antonio Breast Cancer Symposium, 8-12th December, USA
Interview with Dr Dana Faratian (University of Edinburgh, UK)
Systems biology for the clinician
I was talking in an educational session to try and really enlighten clinicians in particular about what the opportunities for systems biology within the clinic might actually be. It was clear from the session that systems biology means different things to different people but what I really aimed to highlight was that whilst systems biology might not be the answer to everything, it certainly does provide some opportunities within the clinic to help us personalise medicine, in particular for breast cancer patients.
The examples I was talking about were not only within the cancer field but also within areas outside cancer. So one of the good examples is where systems biology, so mathematical modelling, has been used to examine electrophysiology of the heart. In that example a systems biology approach, or a mathematical modelling approach, helped drive FDA approval of a particular drug called Ranolazine which helped it go into clinical practice. I think a realistic expectation for breast cancer patients is that similarly these approaches might be used to help us get a little bit more evidence about which drugs might be effective in which patients.
So I was also talking about an example where we looked at some complex signalling pathways in HER2 positive patients and from our mathematical analysis we established that one of the key proteins in these signalling pathways, a well-known tumour suppressor protein called P10, when abnormally regulated was the key determinant of therapeutic response in vitro. Then we went and made these measurements quite carefully in real tissue specimens and established that this protein was also a potential determinant of response in real breast cancer patients to the drug Herceptin.
So this isn’t the answer to everything, so this isn’t mathematical modelling allowing us to get all the answers to cancer but what it does say is where should we look most in terms of a particular biomarker which might determine sensitivity or response to a particular targeted therapy? And that’s useful or potentially useful for clinical trial design.
What is ‘systems biology’?
Systems biology is a framework for thinking about the complexity of a particular biological process. I suppose the term had been coined by one of the forefathers of systems biology, called Dennis Noble, who worked in the field of particularly examining heart physiology. What systems biology means, it defies definition but at least partially at the heart of the definition, or part of an explanation, is that it tells us that biology is more than just the sum of its parts. That makes sense because biology is complex and therefore when we start to understand the interactivity between the components of a particular biological process such as a cancer then we realise that it doesn’t always behave in a predictable way and this, at least in part, is due to the systems level properties of the tumour.
To other people systems biology means integrating a lot of data and clearly there’s a lot of data coming out of all the high throughput studies which are performed on cancer and systems allows us to make some sense of that. But I would argue that what systems really offers us is the ability to look at things over time, so there’s also a dynamic component to systems biology which allows us to understand the behaviour of disease over time. In that respect, mathematical models become useful in order to describe biology over time.
So could this save money in drug development?
I think there’s a potential in terms of rational drug design and also drug development and biomarker development. It means that there is potential for computational or in silico screening of particular processes which might point to a particular place to look and therefore give a level of evidence which would drive a clinical trial design in a particular direction.
The second aspect of applying a systems biology approach is that it demands quite careful quantification. Therefore the types of measurements that are performed, often in real tissue samples, demand a higher level of quantification than perhaps we’ve been used to doing in traditional clinical practice such that techniques that pathologists such as myself use, like immunohistochemistry, might have to be modified to become more quantitative and in doing so we might learn more about the biology of the disease.
Should this be standard practice?
It perhaps, arguably, is already a standard practice. A lot of the major pharmaceutical companies are starting to employ systems biology approaches, or have employed systems biology approaches, in their drug development programmes or biomarker development programmes. So systems biology is a reality for most people. For your average practising pathologist or oncologist it might take a bit of time for some of these approaches to be adopted.
