Flavonoids are polyphenols that are found in numerous edible plant species. Data obtained from preclinical and clini-cal studies suggest that specific flavonoids are chemo-preventive and cytotoxic against various cancers via a multi-tude of mechanisms. However, the clinical use of flavonoids is limited due to challenges associated with their effective use, including (1) the isolation and purification of flavonoids from their natural resources; (2) demonstration of the effects of flavonoids in reducing the risk of certain cancer, in tandem with the cost and time needed for epidemiologi-cal studies, and (3) numerous pharmacokinetic challenges (e.g., bioavailability, drug–drug interactions, and metabolic instability). Currently, numerous approaches are being used to surmount some of these challenges, thereby increas-ing the likelihood of flavonoids being used as chemo-preventive drugs in the clinic. In this review, we summarize the most important challenges and efforts that are being made to surmount these challenges.

Introduction:ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10 (ABCC10) proteins are efflux transporters that couple the energy derived from ATP hydrolysis to the translocation of toxic substances and chemotherapeutic drugs out of cells. Cabazitaxel is a novel taxane that differs from paclitaxel by its lower affinity for ATP-binding cassette (ABC) transporters.
Methods:We determined the effects of cabazitaxel, a novel tubulin-binding taxane, and paclitaxel on paclitaxel-resistant, ABCB1-overexpressing KB-C2 and LLC-MDR1-WT cells and paclitaxel-resistant, ABCC10-overexpressing HEK293/ABCC10 cells by calculating the degree of drug resistance and measuring ATPase activity of the ABCB1 transporter.
Results:Decreased resistance to cabazitaxel compared with paclitaxel was observed in KB-C2, LLC-MDR1-WT, and HEK293/ABCC10 cells. Moreover, cabazitaxel had low efficacy, whereas paclitaxel had high efficacy in stimulating the ATPase activity of ABCB1, indicating a direct interaction of both drugs with the transporter.
Conclusion:ABCB1 and ABCC10 are not primary resistance factors for cabazitaxel compared with paclitaxel, suggesting that cabazitaxel may have a low affinity for these efflux transporters.