The combined action of suicide gene exosomes from pancreatic cancer-associated fibroblasts and from mesenchymal stem cells as a pancreatic ductal adenocarcinoma treatment approach

Exosomes from pancreatic cancer-associated fibroblasts and mesenchymal stem cells that have been transduced with the yeast cytosine deaminase::uracil phosphoribosyl transferase release suicide gene exosomes acting as "Trojan horse" drugs, effectively killing pancreatic cancer cells by converting the non-toxic prodrug 5-fluorocytosine intracellularly into the cytotoxic 5-fluorouracil. We have shown in experiments in vitro, involving a simulated desmoplastic pancreatic tumor, that the combined action of these targeted exosomes could be an approach for pancreatic ductal adenocarcinoma treatment.

经转染酵母胞嘧啶脱氨酶::尿嘧啶磷酸核糖转移酶（yeast cytosine deaminase::uracil phosphoribosyl transferase）的胰腺癌相关成纤维细胞与间充质干细胞，可释放携带自杀基因的外泌体（Exosomes），这类外泌体作为"特洛伊木马（Trojan horse）"型药物，通过在细胞内将无毒前药（prodrug）5-氟胞嘧啶（5-fluorocytosine）转化为具有细胞毒性的5-氟尿嘧啶（5-fluorouracil），从而有效杀伤胰腺癌细胞。我们在体外（in vitro）模拟促结缔组织增生性胰腺癌（desmoplastic pancreatic tumor）的实验中证实，这类靶向外泌体的联合作用可作为胰腺导管腺癌（pancreatic ductal adenocarcinoma）的一种治疗策略。