Poly-pharmacology of existing drugs: How to crack the code?

Drug development in oncology is highly challenging, with less than 5% success rate in clinical trials. This alarming figure points out the need to study in more details the multiple biological effects of drugs in specific contexts. Indeed, the comprehensive assessment of drug poly-pharmacology can p...

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Bibliographic Details
Published in:Cancer letters 2024-04, Vol.588, p.216800-216800, Article 216800
Main Authors: Mouysset, Baptiste, Le Grand, Marion, Camoin, Luc, Pasquier, Eddy
Format: Article
Language:English
Subjects:
Chemo-genomics
Chemo-proteomics
Drug poly-pharmacology
Functional genomics screen
High-throughput drug screening
Life Sciences
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Summary:Drug development in oncology is highly challenging, with less than 5% success rate in clinical trials. This alarming figure points out the need to study in more details the multiple biological effects of drugs in specific contexts. Indeed, the comprehensive assessment of drug poly-pharmacology can provide insights into their therapeutic and adverse effects, to optimize their utilization and maximize the success rate of clinical trials. Recent technological advances have made possible in-depth investigation of drug poly-pharmacology. This review first highlights high-throughput methodologies that have been used to unveil new mechanisms of action of existing drugs. Then, we discuss how emerging chemo-proteomics strategies allow effectively dissecting the poly-pharmacology of drugs in an unsupervised manner. •Poor target validation and lack of biomarkers lead to high rate of drug attrition.•Compound-centric and functional genomic screens can identify cancer vulnerabilities.•Chemo-proteomics can unveil the poly-pharmacology of drugs.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2024.216800