The effect of ABCB1 genetic variants on chemotherapy response in HIV and cancer treatment

Abstract

Despite their clearly distinct pathophysiologies, HIV and cancer are diseases whose response to chemotherapy treatment varies substantially amongst patients, in particular for those with prior drug exposure. This has been attributed, in part, to elevated expression of the ABCB1 drug transporter in some patients, which results in reduced drug accumulation in target tissues. Many mechanisms have been identified for this elevated expression of ABCB1, including variations in the sequence of the gene coding for the transporter (ABCB1). Over 50 SNPs within ABCB1 have been identified. Associations have been made between the presence of specific ABCB1 SNPs/haplotypes and both ABCB1 expression and the efficacy or toxicity of certain chemotherapy regimens. If these associations are strong and reproducibly demonstrated, then this would greatly aid in the development of individualized therapy regimes for specific cancer or HIV patients, based on their ABCB1 genotypes. This article highlights the significant recent progress made in this direction, but cautions that the utility of ABCB1 gene variants as biomarkers of chemotherapy drug response remains unclear to date.