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Synergism or mirage: Current progress and an empirical approach for elucidating combination drug effects

Abstract

In the context of the multitarget paradigm, fixed-dose combination (FDC) drugs, that is, compounds that synergistically target multiple sites when combined, have gained attention for treating complex diseases like cancers and viral infections, as traditional single-drug approaches are often inadequate. This review examines current methods for evaluating and predicting drug synergism in advancing combination drug discovery, highlighting their limitations and providing a unified mathematical framework. Additionally, we present a novel solution to resolve these limitations and improve synergism evaluation, demonstrated through a case study with 20 pairs of FDA-approved chemotherapy drugs for colorectal cancer.

Keywords: combination therapy; complex diseases; drug discovery; drug synergism; multitarget paradigm.

Written by Paola VotteroJack TuszynskiYun K TamChih-Yuan Tseng and originally posted on National Library of Medicine. Link to original article.

https://pubmed.ncbi.nlm.nih.gov/40383289