2021 Early Detection Innovation Grant - Dr Chamini Perera

Project Summary

The holy grail for improving outcomes in pancreatic cancer (PC) is early diagnosis. Diabetes is associated with PC and over one in three patients report a history of recent-onset diabetes (diabetes diagnosed within 3 years prior to their diagnosis of PC, termed pancreatic cancer-related diabetes, PCRD), suggesting PCRD may be a harbinger of PC. It is also well recognised that diabetes facilitates cancer progression. Thus, could this cohort/subset of patients with PCRD benefit from closer surveillance for early detection thereby improving their survival outcome? PC originates from pre-malignant lesions called pancreatic intraepithelial neoplasms (PanINs), which are surrounded by activated pancreatic stellate cells (PSCs, which produce the collagenous stroma of PC). The project team postulates that PanINs and PSCs, secrete factor(s) that are carried via exosomes to i) islet cells, where they inhibit islet cell function, and ii) peripheral cells where they interfere with insulin signalling causing peripheral insulin resistance. The resulting hyperglycaemia/diabetes drives further PSC activation and progression of cancer. The team has demonstrated that exosomes from mouse PC cells and PSCs significantly inhibit insulin secretion by β cells. Given the significant role of RNAs in diabetes and PC, the project team aims to characterise the exosomal RNA cargo and identify potential biomarkers for early detection of pancreatic cancer.