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Three main types of overexpressed ATP-binding cassette (ABC) transporters are strongly involved in tumor resistance to anticancer drugs by pumping out the chemotherapeutics: P-glycoprotein/ABCB1, breast cancer resistance protein/ABCG2 and multidrug resistance (associated) protein/ABCC 1.For well-known ABCB1, some third-generation inhibitors are under advanced clinical development.For more recently discovered ABCG2, screening of series of flavonoids and derivatives as inhibitors of mitoxantrone efflux from transfected HEK293 human cells by flow cytometry, and as chemosensitizers of cell proliferation, allowed us to establish 3D-Quantitative Structure-Activity Relationships (3D-QSARs).