Combinational therapy,which integrates two or more active drugs to overcome diverse therapeutic challenges,is increasingly recognized as more effective than monotherapies(single-drug treatments)for many diseases.(1)Ho...Combinational therapy,which integrates two or more active drugs to overcome diverse therapeutic challenges,is increasingly recognized as more effective than monotherapies(single-drug treatments)for many diseases.(1)However,the subcellular site where each drug acts is a crucial determinant of whether their combined effect will be synergistic or antagonistic.(2,3)Certain therapeutics target intracellular components(e.g.,the nucleus,mitochondria,endoplasmic reticulum,Golgi apparatus,or cytosolic signaling pathways),whereas others act on membrane-associated structures such as lipids,glycans,or proteins.(4−6)Maximizing the efficacy of such combination regimen thus requires delivering each component to its appropriate subcellular site.For example,a membrane-acting antibody must remain on the cell surface,whereas an enzyme inhibitor intended for a cytosolic pathway needs to reach the intracellular environment.If either drug misses its target location,the therapeutic outcome can be compromised.展开更多
基金supported by the National Key Research and Development Program of China(2024YFA1212100,2025YFE0114200)the National Natural Science Foundation of China(52422318,52373166,52573162,22277155,32471423)+2 种基金the Natural Science Foundation of Guangdong Province for Distinguished Young Scholar(2024B1515020025)the Guangdong Basic and Applied Basic Research Foundation(2025A1515010524)the Science and Technology Program of Guangzhou(2024A04J6572,2025A04J7161,2025A04J1327),and the China Primary Health Care Foundation(2022-003).
文摘Combinational therapy,which integrates two or more active drugs to overcome diverse therapeutic challenges,is increasingly recognized as more effective than monotherapies(single-drug treatments)for many diseases.(1)However,the subcellular site where each drug acts is a crucial determinant of whether their combined effect will be synergistic or antagonistic.(2,3)Certain therapeutics target intracellular components(e.g.,the nucleus,mitochondria,endoplasmic reticulum,Golgi apparatus,or cytosolic signaling pathways),whereas others act on membrane-associated structures such as lipids,glycans,or proteins.(4−6)Maximizing the efficacy of such combination regimen thus requires delivering each component to its appropriate subcellular site.For example,a membrane-acting antibody must remain on the cell surface,whereas an enzyme inhibitor intended for a cytosolic pathway needs to reach the intracellular environment.If either drug misses its target location,the therapeutic outcome can be compromised.
