Engineered cyclic peptide targeting ITGA5 disrupts tumor-stroma interaction to overcome desmoplasia and resistance in pancreatic ductal adenocarcinoma

The tumor-stroma interaction contributes to the aggressive and resistance nature of pancreatic ductal adenocarcinoma (PDAC), leading to treatment failure. Cancer-associated fibroblasts (CAFs), a key cell type in the stroma, produce abundant extracellular matrix (ECM) and exhibit crosstalk with cancer cells inducing chemoresistance. In this study, we designed a cyclic peptide (cyAV3.3) targeting integrin α5 (ITGA5) to disrupt CAF-induced desmoplasia and crosstalk with cancer cells. In vitro,...