Title:Polypharmacology in Precision Oncology: Current Applications and Future Prospects
VOLUME: 22 ISSUE: 46
Author(s):Albert A. Antolin, Paul Workman, Jordi Mestres and Bissan Al-Lazikani
Affiliation:Division of Cancer Therapeutics, The Institute of Cancer Research, London
Keywords:Polypharmacology, systems pharmacology, off-target, precision oncology, biomarker, target profiling, side-effects, multi-target
drug design.
Abstract: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.
