Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years

Figure 5 Irinotecan is metabolized to APC or NPC and potential other intermediate metabolites (M1, M2) via a cytochrome P450 mediated process. Neither 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC) nor 7-ethyl-10-(4-amino-1-piperidino)carbonyloxycamptothecin (NPC) contribute directly to irinotecan activity in vivo. NPC is further converted to 7-ethyl-10-hydroxy-camptothecin (SN-38) by carboxylesterase. All irinotecan metabolites are pH sensitive, thus are at risk of transforming from inactive to active products, and vice versa. SN-38 is subsequently conjugated predominantly by the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) to form a glucuronide metabolite (SN-38G)[403].