Pancreatic Ductal Adenocarcinoma: MicroRNAs Affecting Tumor Growth and Metastasis in Preclinical In Vivo Models

Abstract

Patients with pancreatic ductal adenocarcinoma have a dismall prognosis because at the time of diagnosis, in the vast majority of patients the tumor has already disseminated to distant organs and the therapeutic benefit of approved agents such as gemcitabine is limited. Therefore, the identification and preclinical and clinical validation of therapeutic agents covering new targets is of paramount importance. In this review we have summarized microRNAs and corresponding targets which affect growth and metastasis of pancreatic tumors in preclinical mouse in vivo models. We identified four up-regulated and 16 down-regulated miRs in PDAC in comparison to corresponding normal tissues. Three sub-categories of miRs have emerged: miRs affecting tumor growth and miRs with an impact on both, tumor growth and metastasis or metastasis only. Finally, we discuss technical and therapeutic aspects of miR-related therapeutic agents for the treatment of pancreatic ductal adenocarcinoma.

Keywords: Antagomirs; KRAS oncogene; miR sponges; orthotopic xenograft models; review; therapeutic miR-related agents; transforming growth factor β signaling; tumor suppressor genes.