ABC transporter genetic polymorphisms in cancer therapy: implications for anticancer drug disposition, efficacy, and toxicity

Introduction Pharmacogenetics has emerged as an important component of precision medicine in oncology. Although clinical implementation has primarily focused on established biomarkers, such as DPYD, UGT1A1, TPMT, and NUDT15, data suggests that genetic variations in ATP-binding cassette (ABC) drug transporters may also affect the disposition and clinical effects of anticancer therapies. This review summarizes current evidence regarding the contribution of ABCB1, ABCC1, and ABCG2 polymorphisms to anticancer therapy’s efficacy and toxicity. Methods and Materials A narrative review of the published pharmacogenetic and pharmacokinetic literature was conducted, focusing on studies evaluating germline polymorphisms in ABC transporter genes and their associations with anticancer drug disposition, treatment efficacy, and adverse events. Results ABC transporter polymorphisms have been associated with clinically relevant variability in anticancer drug efficacy and toxicity. The effects of variants in ABCB1, particularly C1236T, G2677 T/A, and C3435T, on taxane- and anthracycline-induced toxicity and treatment response have been extensively studied. ABCC1 variants have been associated with vincristine-induced peripheral neuropathy and with hematologic, gastrointestinal, hepatic, and cardiac toxicities following anthracyclines and other chemotherapy regimens. ABCG2 polymorphisms, particularly C421A, have demonstrated associations with drug exposure and toxicity for selected tyrosine kinase inhibitors, among other therapies. Conclusion Variations in ABC transporter genes represent a potentially important factor that contributes to variability in anticancer drug response and toxicity. Our heterogeneous findings emphasize that transporter-mediated drug disposition is multifactorial; therefore, future research should prioritize the use of polygenic models that integrate pharmacogenomics with other tumor- and patient-specific factors to better understand the relationship between ABC transporter polymorphisms and anticancer drugs, and how these genetic variants affect drug efficacy and toxicity.