Table 1.

Overview of the current knowledge regarding drug-transporter-mediated TKI efflux. Direct evidence is defined as assays where overexpression of a drug transporting protein resulted in reduced intracellular TKI concentrations; all other assay types are listed as indirect evidence.

Compound	Drug Transporting Protein	Direct/Indirect Evidence	Readout	Source
Imatinib	P-gp	Indirect	Increased intracellular uptake and retention in P-gp overexpressing LLC-PK1 cells upon addition of the specific P-gp inhibitor cyclosporin A.	[85]
	BCRP	Direct	Decreased imatinib uptake in BCRP overexpressing cell lines and increased intracellular uptake and retention upon addition of the specific BCRP inhibitor Ko-143.	[93]
	ABCC3	Direct	Increased efflux in ABCC3 overexpressing MDCKII cell monolayers that could be nullified by the addition of the ABCC3 inhibitor probenecid.	[101]
	ABCA3	Indirect	Enhanced transporter expression in CD34+ BCR::ABL1+ leukemic cells after imatinib exposure.	[104]
Nilotinib	P-gp	Indirect	No evidence of radiolabeled nilotinib efflux in P-gp overexpressing MDCKII cells, but significant upregulation of P-gp expression in nilotinib resistant K562 cells.	[54,114]
	BCRP	Indirect	BCRP overexpression in K562 cells protects against nilotinib-mediated cell death.	[46,113]
	ABCA3	Indirect	Enhanced transporter expression in CD34+ BCR::ABL1+ leukemic cells after nilotinib exposure.	[104]
Dasatinib	P-gp	Direct	Reduced intracellular uptake and retention of dasatinib in P-gp overexpressing K562 cells, which could be reversed by a specific P-gp inhibitor.	[113,124]
	BCRP	Direct	Reduced intracellular uptake and retention of dasatinib in BCRP overexpressing K562 cells, which could be reversed by a specific BCRP inhibitor.	[113,124]
	ABCA3	Indirect	Enhanced transporter expression in CD34+ BCR::ABL1 leukemic cells after dasatinib exposure.	[104]
Bosutinib	P-gp	Indirect	Lower intracellular uptake and retention of bosutinib in P-gp overexpressing K562 cells and reduced BCR::ABL1 phosphorylation upon co-treatment of bosutinib and a specific P-gp inhibitor. However, P-gp overexpression had no effect on bosutinib-mediated cellular toxicity.	[113,138]
	BCRP	Indirect	Minor protective effect against bosutinib treatment in BCRP overexpressing K562 cells.	[113]
Asciminib	P-gp	Indirect	Decreased asciminib-mediated cell death in P-gp overexpressing K562 cells, which was nullified upon inhibition of P-gp.	[144,145]