Fatty acid synthase, a novel drug target for the treatment of drug resistant breast cancers Free

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Use of anticancer agents in appropriate combinations has led to major improvements in the treatment of malignant tumors. Despite such successes, resistance to chemotherapy frequently occurs and is a major obstacle in successful treatment of cancers. Studies with model tumor cell lines have revealed that multidrug resistance (MDR) can develop and, thus, causes chemotherapy failure. Recently, we found that fatty acid synthase (FAS) expression was drastically elevated in a series of drug-resistant breast cancer cell lines selected with Adriamycin using proteomic approach. Down-regulation of FAS expression in the drug resistant breast cancer cell lines using siRNA reversed the drug resistance phenotype and ectopic over-expression of FAS in the parental drug sensitive MCF7 cells increased the resistance. Interestingly, down-regulation of FAS expression level in normal mammary epithelial MCF10A1 cells did not affect their response to anticancer drugs. These observations suggest that FAS is a good target for chemosensitization of breast cancers using combinational therapy.