Oncogenic Signalling Networks and Polypharmacology as Paradigms to Cope with Cancer Heterogeneity
Aurelio A. Moya García,
Juan Juan A.G. Ranea.
The large collection of mutated genes in the cancer genome mapping onto a reduced set of signalling pathways
highlights the paramount importance of signalling pathways in cancer therapeutics. Signalling proteins operate through a
large and complex network associated with cell properties and ultimately reprogrammed in order to implement the known
hallmark capabilities in cancer cells. Overall the underlying connection between signalling networks and the hallmarks of
cancer may be considered as an organising principle that fixes the framework for understanding the remarkable diversity
of this disease.
There is a growing body of evidence suggesting that drug polypharmacology is the rule rather than the exception to overtake
the limited success obtained in clinical treatment of cancer. Further the need for multi-target approaches, the combination
between network pharmacology and polypharmacology is shifting the specific targeted drugs paradigm. In this
novel systemic paradigm the dysregulated signalling networks themselves emerge as a class of targetable entities. Diverse
cancer types and even a heterogeneous cellular population within a cancer type may exhibit heterogeneity in their signalling
networks. We review these emerging trends in the field of computational and systems biology to achieve a more effective
and safer control of cancer.
Keywords: Cell signalling, oncogene, polypharmacology, signalling network, signalling pathway, tumour heterogeneity.
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