| There are two major problems in cancer chemotherapy. One is the innate or acquired resistance of cancer cells to anticancer drugs, and the other is the toxicity of the chemotherapeutic drugs to certain normal tissues, such as bone marrow. The study of the mechanisms of drug resistance in cancer cells has led to the identification of some of the genes and gene products that confer drug resistance. In particular, ABC transporters such as P-glycoprotein (ABCB1, MDR1 gene product), MRPs (ABCCs), and BCRP (ABCG2) act as ATP-dependent efflux pumps for various structurally unrelated natural product antitumor agents. Expressions of such transporters in normal and tumor tissues are key determinants for innate or acquired drug resistance of cancer cells and toxicity of normal cells. Our study is therefore focused on (1) drug resistance gene therapy to potect normal hematopoietic cells from the toxic effect of anticancer agents. (2) mechanism of drug resistance, (3) circumvention of drug resistance, and (4) pharmacogenomics and pharmacodynamics related to drug transporters. |
