Title: Human carboxylesterase 2 is commonly expressed in tumor tissue and is correlated with activation of irinotecan Xu G, Zhang W, Ma MK, McLeod HL Ref: Clin Cancer Research, 8:2605, 2002 : PubMed
The prodrug irinotecan is an active agent for the treatment of advanced colorectal cancer and a number of other solid tumors. Irinotecan is converted in vivo to SN-38 (7-ethyl-10-hydroxy-camptothecin), the active metabolite that causes cell death, by human liver carboxylesterases. Previous studies suggest that human carboxylesterase 2 (CES2) is the key activating isoform. Although conversion of irinotecan to SN-38 by liver carboxylesterase is an inefficient process, clinical data indicate that irinotecan has significant antitumor activity. This scenario raises the possibility that local conversion of irinotecan to SN-38 by CES2 in tumor tissues might occur. The expression profile of CES2 protein in human tumor tissues was evaluated in a tissue array of 18 different types of human cancer and in a panel of normal human liver samples by immunohistochemistry and Western blot, respectively. Cytosolic CES2 expression was observed in 101 of 154 tumors (66%) and 55 of 60 normal tissues (92%). Among the 18 types of tumors analyzed, 2 types (gallbladder tumor and lymphoma) did not express CES2, 5 types expressed weak CES2, and 11 types expressed moderate to intense CES2. In functional studies, CES2 protein was highly variable among liver samples, with a 15-fold range in cytosol and a 3-fold range in microsome fractions. Liver microsomal CES2 protein expression was significantly correlated with irinotecan activation to SN-38 (R(s) = 0.70; P = 0.007). This study confirms that CES2 is a key enzyme for irinotecan activation. Tumor CES2 expression may contribute to variable response to irinotecan chemotherapy for solid tumors.
        
Related information
Citations formats
Xu G, Zhang W, Ma MK, McLeod HL (2002) Human carboxylesterase 2 is commonly expressed in tumor tissue and is correlated with activation of irinotecan Clin Cancer Research8: 2605-11
Xu G, Zhang W, Ma MK, McLeod HL (2002) Clin Cancer Research8: 2605-11