| Growth Factors Whether cells divide, remain quiescent or die depends critically on the availability of nutrients and extracellular growth factors. Cancer develops when cells divide inappropriately, or do not die appropriately, this in turn frequently being due to aberrations in the growth factor signaling pathways that control the balance between division and death. Although Physiomics has developed detailed models of cell proliferation and cell death, we are also currently building models of growth factor signaling. Our growth factor signaling models provide the capability of simulating the changes in survival signaling pathways that contribute to the development of cancer, as well as anti-cancer drugs that specifically target growth factor pathways (e.g. Herceptin against HER receptors, AstraZeneca’s Iressa, Genentech’s/OSI’s tarceva, and the raf inhibitor ZM3363732). The model currently being developed by Physiomics is based on the published model of MAP-kinase signalling by Brightman and Fell (Brightman, F., A., Fell, D. A. FEBS Letters 482 (2000) 169-174). An outline of the model is shown below:
The growth factor signalling model running together with our cell cycle and apoptosis models provides us with the powerful capability of simulating the mechanisms controlling the balance between proliferation and cell death, including many of the mutations that occur in these pathways that lead to cancer and determine the sensitivity of the tumour to different therapeutic strategies. Moreover, these models running in a cell population environment, SystemCell® technology, form a vital component of our Virtual Tumour simulations, powerful in silico representations of the response of tumours to different anti-cancer drugs over clinical treatment times.
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