Systems biology: shaping the future of breast cancer treatment

Intro text: 


We now understand the uniqueness of each tumour. However, the deeper we dig into tumour heterogeneity, the more complex is our fight against cancer. How is it possible to identify, for each patient, the specific molecular aberrations that cause and maintain the tumour? How, among the thousands of possible combinations of targeted drugs, do we find the most appropriate and logical one that will lead to cancer cell death? How, at the end of the day, can we predict which treatment strategy will work best for each individual patient?

In this 3rd issue of BIG's scientific publication BIG Research in focus, experts from Europe and the US focus on the many challenges and questions raised by the systems biology techniques and their potential translation into clinic.

Read the insights from Professors Gordon Mills (University of Texas MD Anderson Cancer Center, USA), David Cameron (Edinburgh Cancer Research Centre, UK), Andrea Califano (Columbia University, USA) and Christopher Lord (Institute of Cancer Research, UK) who tell us more about this systems biology approach that will hopefully guide researchers towards more rational clinical testing, better treatment strategies and more effective cures for the patients.

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Here is a short extract of the article:

Systems biology involves building mathematically based models of the functional consequences of changes to intracellular networks that occur during or after carcinogenesis – not only in isolation, but also within the context of the local microenvironment and the larger physiological ecosystem. In breast cancer, as in many other forms of the disease, the systems biology approach is expected to pay dividends in shaping rational combinations of targeted drug therapies and predicting patient response to treatment.  Jenny Bryan reports research and clinical perspectives on the potential of systems biology for future advances in breast cancer care. 

Building a complete picture of the most important genetic mutations and abnormal protein behaviour in a cancer cell within the broader physiological ecosystem and predicting the likely impact of drug interventions sounds like mission impossible. But a powerful coalition of biological scientists, mathematicians and clinicians has not only accepted the challenge, but is well on the way to completing the mammoth task.
Essential to the success of the mission is the bringing together of a number of cutting edge biological and computational technologies that facilitate the collection and analysis of huge amounts of experimental data emerging from the fledgling specialty of systems biology. 

Professor Gordon Mills, who started the first department of cancer systems biology at the University of Texas MD Anderson Cancer Center in Houston, USA, predicts that the rational use of systems biology will have a major impact in identifying better ways of treating patients with cancer:  

“Having spent 20 years trying to draw arrows in signalling pathways, I realised that those arrows, though important, did not explain how the system worked in context and that we needed a new approach. Systems biology is going to play an absolutely critical role in how we combine targeted therapies rationally and with immunotherapies to give us a more efficient way of moving forward, instead of trying every two-by-two combination we can think of, without predicting who is likely to benefit.” 

As a clinician currently using predictive tests for breast cancer treatment based on mutations in up to 70 individual genes, Professor David Cameron, Clinical Director and Chair of Oncology at the Edinburgh Cancer Research Centre, in Edinburgh, UK, welcomes the potential for the more integrated approach offered by systems biology.  
“The new technologies are revealing much more information about what is going on in cancer cells and how the cancer interacts with the patient, though we are not yet at the point of using the constructs generated by systems biology in the clinic. But I am hoping that, in perhaps five years, we will be able to compare test results in our patients with known biological insights and algorithms generated by systems biology to understand what is happening in each patient’s tumour,” says Professor Cameron.
Like Professor Mills, he hopes that systems biology will enable new drug combinations to get to the clinic more quickly, thanks to faster, more logical clinical testing.

“We have enough different drugs coming through, targeting different pathways, to be able to construct the drug combinations we need to tackle cancer biology but if we put them together randomly we’ll have potentially thousands of combinations to get through,” says Professor Cameron. “Hopefully, systems biology will allow us to combine drugs more logically and rapidly, based  on a better understanding not only of how the cancer is behaving before we started treating it, but also how it has adapted to the treatment we’ve already given.”

Writer: Jenny Bryan