New trends for overcoming ABCG2/BCRP-mediated resistance to cancer therapies

Table 1 Brief summary of anti-cancer compounds that are ABCG2 substrates

Compound	Mechanism of action	Note (see below)	Reference
Traditional cytotoxics
Mitoxantrone	Topoisomerase II poison		[4]
Etoposide	Topoisomerase II poison		[11, 12]
Doxorubicin	DNA intercalator; Topo II poison	1	[27, 29]
Daunarubicin	DNA intercalator; Topo II poison	1	[27, 29]
Epirubicin	DNA intercalator; Topo II poison	1	[29]
Topotecan	Topoisomerase I poison		[22]
Irinotecan	Topoisomerase I poison		[27]
SN-38	Topoisomerase I poison	2	[21]
5-fluorouracil	Thymidylate synthase inhibitor		[26]
Methotrexate	Dihydrofolate reductase inhibitor		[24]
Cladribine	Nucleoside analogue		[28]
Clofarabine	Nucleoside analogue		[28]
6-mercaptopurine	Nucleoside analogue		[28]
Flavopiridol	CDK9 inhibitor		[25]
Tyrosine kinase inhibitors
Imatinib	Bcr-Abl inhibitor		[13, 89]
Dasatinib	Bcr-Abl inhibitor	3	[14, 40]
Nilotinib	Bcr-Abl inhibitor		[14]
Sorafenib	Multi-kinase inhibitor	4	[91, 93]
Sunitinib	Multi-kinase inhibitor	5	[87, 92]
Gefitinib	EGFR inhibitor		[15]
Erlotinib	EGFR inhibitor		[16]
Rucaparib	PARP inhibitor	6	[37, 38]
PDT agents
Pheophorbide a	Photosensitizer		[39]
Chlorin e6	Photosensitizer		[41]
HPPH	Photosensitizer		[42, 43]
5-aminolevulinic acid	Photosensitizer		[48]
Porfimer sodium	Photosensitizer	7	[49]

1, Requires gain-of-function mutation at ABCG2 R482
2, SN-38 is the active metabolite of irinotecan
3, One study suggests ABCG2 expression correlates with poor patient response
4, Phase I/II trial of sorafenib plus irinotecan recently completed
5, Phase III trial of sunitinib plus FOLFIRI found no benefit over FOLFIRI alone
6, ABCG2 also limits rucaparib oral bioavailability
7, ABCG2 correlates with poor response to porfimer sodium in NSCLC patients

ISSN: 1756-9966