| 研究実績の概要 |
In order to identify establish an integrative framework to identify alternative or combinatorial therapeutic strategies to overcome drug resistance of cancer cells. We first attempted to develop an analytic framework that can dissect the effects of drugs at pathway level. Based on this framework, we can identity unexpected effects of drugs which could be adverse effects or new usages. We selected statins, commonly used for lowering cholesterol levels, as an example to evaluate our framework. Several studies have suggested that statins may have potential as cancer therapy in human malignancies, including liver cancer 15,16, breast cancer, and leukemia. In contrast, some studies revealed that statins increase cancer risk of prostate cancer. In addition, there are other adverse effects of statins that have been identified in recent years, for example, increased risk of early-onset of type II diabetes. However, the details of the mechanisms of these unexpected effects, whether positive or negative, are still not clear. Applying our framework to treatment of three different cell types with four widely used statins, we identify significantly associated pairs of transcriptional factors and pathways, and infer regulatory networks to elucidate the regulation of on-/off-target pathways. We show that our framework provides new insights about the effect of the drugs under study, and helps identification of new usages or potential side effects.
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