90
F. Cheng
Fig. 5.5 Proposed mechanistic model of imatinib-induced cardiotoxicity. A highlighted subnetwork shows the predicted mechanism-of-action for imatinib-induced cardiotoxicity by drug-target
network analysis under the human protein-protein interactome model. Imatinib’s targets were collected from the DrugBank database [53]. The human protein-protein interactions and the known
cardiovascular disease genes were collected from bioinformatics resources as described in Table 5.2
5.4 Conclusion and Future Directions
In this chapter, we introduce a network-based, systems pharmacology approach for
quantifying drug-disease associations under the human protein-protein interactome
network model as developed recently [48]. This network-based approach can be
used for drug repurposing or for risk assessment of drug-induced cardiotoxicity. We
showcased that this network-based, systems pharmacology approach can be used
to identify well-known cardio-toxic chemotherapeutic agents and novel oncological
drug-induced cardiotoxicities.
We acknowledge several potential limitations in the current systems pharmacology framework. The total size of the human protein-protein interactome is estimated
to be ~650,000 interactions [95]. Data incompleteness of the human interactome and
known drug-target networks should be of concern. In addition, potential literature
F. Cheng
Fig. 5.5 Proposed mechanistic model of imatinib-induced cardiotoxicity. A highlighted subnetwork shows the predicted mechanism-of-action for imatinib-induced cardiotoxicity by drug-target
network analysis under the human protein-protein interactome model. Imatinib’s targets were collected from the DrugBank database [53]. The human protein-protein interactions and the known
cardiovascular disease genes were collected from bioinformatics resources as described in Table 5.2
5.4 Conclusion and Future Directions
In this chapter, we introduce a network-based, systems pharmacology approach for
quantifying drug-disease associations under the human protein-protein interactome
network model as developed recently [48]. This network-based approach can be
used for drug repurposing or for risk assessment of drug-induced cardiotoxicity. We
showcased that this network-based, systems pharmacology approach can be used
to identify well-known cardio-toxic chemotherapeutic agents and novel oncological
drug-induced cardiotoxicities.
We acknowledge several potential limitations in the current systems pharmacology framework. The total size of the human protein-protein interactome is estimated
to be ~650,000 interactions [95]. Data incompleteness of the human interactome and
known drug-target networks should be of concern. In addition, potential literature