2023 New Treatment Grant - Dr Enyuan Cao

Project Summary

Pancreatic cancer (PDAC) is one of the most lethal types of human cancer due to its aggressive nature and lack of effective treatments. Obesity further increases cancer risk by altering the metabolism of cancer cells. Sadly, enormous efforts in treatment development have not yet improved the survival rate nor the off-target effects. New therapeutic targets and treatments are critically needed. >70% of pancreatic cancers originate from the head of the pancreas, where the pancreas is connected to both the gut and adipose tissue. However, the factors that promote cancer formation in this area are unknown, and no clinically relevant model recapitulatesthis key pathological feature of PDAC. Our data reveal a previously undescribed crosstalk between the gut-draining lymphatics and pancreas where, especially in obesity, lymphaticssupplies energy source in the form of dietary lipids to the pancreas which modifies cancer cell metabolism and promote metastasis. We will: 1. Establish the first clinically relevant, PDAC model at the head of the pancreas to investigate the cause of cancer formation. 2. Examine how ‘obesity-associated lipids’ modify cancer metabolism and promote PDAC. 3. Stop PDAC by shutting shown the lymphatic ‘energy supply’ via targeting lymph-pancreas interactions with minimal off-target effects.