Reversal Of BCRP Mediated-Atypical MDR Phenotype By Adenovirus-Delivered RNA Interference

[Background and objective]Human cancer cells can exhibit a cross-resistant phenotype against several unrelated drugs that differ widely with respect to molecular structure and target specificity. This phenomenon has been termed multidrug resistance (MDR). MDR, a common phenomenon in cancer patients, is the major obstacle in the successful treatment of cancer. Although the mechanistic basis for this phenomenon is complex, the overexpression of ABC transporters is often associated with this phenotype. Various members of the protein superfamily of ABC transporters have been associated with MDR of human cancers when overexpressed, including P-gp, the MRP and its homologues MRP2 and MRP3. BCRP is a relatively new member of the ABC-transporter family and overexpressed in a variety of human MDR cancer cell lines. Elevated expression of BCRP results in resistance to antitumor drugs, including mitoxantrone, topotecan, daunorubicin, doxorubicin and bisantrene etc.Reversal of MDR is a major goal in the clinical management of cancer. Pharmacological inhibition of the ABC transporters can be expected to resensitize cells to the action of antitumor agents. Inhibitors of BCRP have been reported. An alternative procedure to circumvent BCRP-mediated MDR...