PMC:4331679 / 4515-6294 JSONTXT

{"project":"2_test","denotations":[{"id":"25707537-22579283-14870712","span":{"begin":156,"end":157},"obj":"22579283"}],"text":"On the other hand, data driven modelling of signalling pathways is a promising approach to uncover regulatory mechanism for cancer cell fate. The study in [5] investigated three lines of breast tumour, namely BT-20, MDA-MB-453 and MCF7, for their responses to various combinations of exposure to several genotoxic drugs and signalling inhibitors. The authors found that it was the pre-treatment, rather than co-treatment or post-treatment, of a subset of TNBCs with Epidermal Growth Factor Receptor (EGFR) inhibitors that can enhance the sensitivity of tumour cells in their apoptosis response to DNA-damaging chemotherapy. The study suggested that such a treatment may lead to the rewiring of oncogenic signalling pathways which has the potential to make cancer cells more susceptible to death. It was further reported that the inhibition of EGFR in a time-staggered way may be responsible for sensitising tumour cells to genotoxic drugs. However, simultaneous co-administration of inhibitors and genotoxic drug could not make the tumour cells less tumorigenic. To test these hypotheses, the study systematically investigated a series of drug combinations for their effects on breast cancer cells. The study suggests that rewiring inside the tumour cells is responsible for the increase of drug sensitivity, but it is not clear where and how the rewiring happens. The rewiring involves alterations of signalling pathways such as addition or deletion of edges in the network, change in reactions rates, and change in the concentration of molecules. Since it is more challenging to directly observe rewiring signalling pathways by wet lab experiments, computational methods for predicting rewiring from data would be useful for study of cancer drug effect and cell fate decisions."}