Among the novel and target-specific classes of anticancer drugs, small molecule
tyrosine kinase inhibitors (TKIs) represent an extremely promising and rapidly expanding group. TKIs attack
cancer-specific targets and therefore have a favorable safety profile. However, as TKIs are taken orally along with other medications on a daily basis, there is an elevated risk of potentially significant
drug-drug interactions. Most TKIs are metabolized primarily through
CYP3A4. In addition, many TKIs are also
CYP3A4 inhibitors at the same time. In addition to
drug metabolizing
enzymes (
DMEs), another determinant of TKI disposition are
drug transporters. There is accumulating evidence showing that the majority of currently marketed TKIs interact with
ATP-binding cassette transporters, particularly
P-glycoprotein as well as
Breast Cancer Resistance
Protein and serve as both substrates and inhibitors. Considering the dual roles of TKIs on both
DMEs and
drug transporters, and the importance of these
enzyme and transporters in
drug disposition, the potential for
enzyme- and transporter-mediated TKI-drug interactions in patients with
cancer is an important consideration. This review provides a comprehensive overview of drug interactions with small molecule TKIs mediated by
DMEs and
drug transporters. The TKI-drug interactions with TKIs being victims and/or perpetrators are summarized.