Polypharmacology in Precision Oncology: Current Applications and Future Prospects.
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Date
2017-01-24Author
Antolin, AA
Workman, P
Mestres, J
Al-Lazikani, B
Type
Journal Article
Metadata
Show full item recordAbstract
Over the past decade, a more comprehensive, large-scale approach to studying cancer genetics and biology has revealed the challenges of tumor heterogeneity, adaption, evolution and drug resistance, while systems-based pharmacology and chemical biology strategies have uncovered a much more complex interaction between drugs and the human proteome than was previously anticipated. In this mini-review we assess the progress and potential of drug polypharmacology in biomarker-driven precision oncology. Polypharmacology not only provides great opportunities for drug repurposing to exploit off-target effects in a new single-target indication but through simultaneous blockade of multiple targets or pathways offers exciting opportunities to slow, overcome or even prevent inherent or adaptive drug resistance. We highlight the many challenges associated with exploiting known or desired polypharmacology in drug design and development, and assess computational and experimental methods to uncover unknown polypharmacology. A comprehensive understanding of the intricate links between polypharmacology, efficacy and safety is urgently needed if we are to tackle the enduring challenge of cancer drug resistance and to fully exploit polypharmacology for the ultimate benefit of cancer patients.
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Subject
Humans
Neoplasms
Antineoplastic Agents
Medical Oncology
Drug Resistance, Neoplasm
Drug Repositioning
Polypharmacology
Research team
Computational Biology and Chemogenomics
Language
eng
Date accepted
2016-09-19
License start date
2016-01
Citation
Current pharmaceutical design, 2016, 22 (46), pp. 6935 - 6945
Publisher
BENTHAM SCIENCE PUBL LTD