Studies on the relation between drug sensitivity and transporters in cancer for tailor-made cancer chemotherapy

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In this study, we revealed the "in vivo drug resistance" in hepatocellular carcinomas and renal cell carcinoma. The cancer cells are resistant to cicplatin only in proliferating in the host, but when they were incubated in vitro, the drug sensitivity is markedly increased. We clarified the mechanisms of the in vivo drug resistance. The cells express several ABC transporters on the plasma membrane, and the expression of MRP2 among transporters was disappeared during in vitro culture and was incresed by addition of conjugated bilirubin. These results strongly suggest when cancer cells are growing in the host, MRP2 induced by bilirubin extrude anticancer drugs including cisplatin and the cancer cells are resistant to the anticancer drugs. On the other hand, the expression level of MRP2 was quite different among cancer specimens from patients. Therefore, estimation of the transporter expression level of cancer biopsy specimens may be very useful for cancer chemotherapy and become the tailor-made chemotherapy.