During the last decade, increasing interest has developed in fatty acid synthase (FAS) as a potential diagnostic and therapeutic target for human cancer. These notions are based on two fundamental observations: [1] FAS is highly expressed in most common human cancers, and [2] pharmacological inhibition of FAS leads to apoptosis of human cancer cells in vitro and in vivo. FAS is the enzyme which catalyzes the de novo synthesis of fatty acids predominantly from dietary carbohydrates. In addition to its expression in human cancers, our collaborators have found that FAS circulates at high levels in the blood of colon, breast, lung, ovarian, and prostate cancer patients compared to normal subjects. Recent data have emerged which directly impact FAS as a biomarker for cancer: [1] FAS elevations have been found to occur in the blood of obese subjects with non-alcoholic steatohepatitis, and [2] FAS derived from tumor cell lines is phosphorylated on threonine residues while FAS from non-transformed cells is not phosphorylated. These findings will enable the development of a diagnostic ELISA serum test for human cancer based on phosphorylated FAS which would not react with FAS derived from normal tissues such as liver. The goals of this Phase I SBIR are to determine that FAS derived from human cancer is selectively phosphorylated and detectable in the serum of cancer patients but not in the sera of obese subjects. This tumor selective phospho-FAS would form the basis for the development of a cancer-selective FAS ELISA assay for the Phase II application. The early diagnosis of cancer enables more effective therapy and enhances patient survival and quality of life. Fatty acid synthase is present at high levels in most common human cancers including colon, lung, prostate and breast cancer. The goal of this proposal is to advance the development of a blood test for cancer based on the identification of FAS which will broadly identify the presence of most human cancer. ? ? ?
