Interestingly, previous studies have shown that selleck bio reduced g secretase and notch1 activity in mice cause a high fre quency of skin cancer and that hidradenitis suppur ativa can be an allelic disorder of early onset familial AD. Indeed, the feature based map of AD, hidrade nitis suppurativa, g secretase inhibitors and tarenflurbil converge on the notch signaling pathway. While the overlap of our discovered drug repositioning candidates with those under clinical trials demonstrates the utility of our approach, it also shows the limitations of computational approaches. In other words, while the computational approaches can provide potential candidates for drug repositioning, it may not be easy to foresee their failure in clinical trials.

Nevertheless, the feature details our approach provides for the disease and candidate drug connectivity may not only help in understanding the molecular basis of side effects but also make more informed decisions. Conclusions Our approach to predict novel indications by representing disease drug combinations as combinations of their mole cular and mechanistic features, including biological pro cesses, pathways, and phenotypes, not only led to the proposal of drug repositioning candidates but also allowed mechanistic insights into them. The robustness of our pre dictions and their overlap with those reported in the litera ture and clinical trials demonstrate that this approach can effectively identify new indications with the enriched fea ture patterns as an indicator for the mode of action.

Although we have looked beyond the gene based relation ships, a limitation of this method is that it relies on the feature patterns enriched in diseases and drugs which themselves are generated using the genes associated with diseases or drugs. Batimastat Thus, diseases and drugs that currently lack gene annotations are left out. Nevertheless, some of the discovered novel indications are far from being obvious and may also help in understanding the molecular basis of side effects. As Novac points out in a recent review, while it is too early to evaluate the success of repositioning efforts, the obvious candidates for reposi tioning may have already been exhausted. Thus, a much more thorough analysis and investment has to be done to reposition the rest of the candidates.

Background Cancer progression is characterized, in part, by altered or aberrant transcription factor function, leading to changes in expression of cancer related genes. Mes enchymal to Epithelial Transition and its mirror process are critical to metastasis in cancer progression. We re cently demonstrated a novel function selleck catalog of the OVOL1 and OVOL2 TFs as critical inducers of MET in pros tate cancer. One of the outcomes of this recent work suggests the hy pothesis that the OVOLs have roles in regulating MET in multiple cancers.