Targeting pancreatic cancer (PC) via anti-fibrotic NID2 therapy and Gemcitabine/Abraxane chemotherapy treatment: stratifying PC therapy
Background
Pancreatic cancer is one of the most lethal forms of human cancer, with more than 90% of patient deaths occurring within 1 year of diagnosis, in part due to surgically unresectable, advanced disease being present at the time of diagnosis. Recent work by Professor Timpson’s team has shown that some patients harbour high levels of fibrosis, making them exquisitely sensitive to anti-fibrotic therapy which can lead to improved delivery of anti-cancer drugs such as chemotherapy. Consequently, the development of more effective strategies to maximise this new opportunity in pancreatic cancer is urgently required.
About the Project
The ability to monitor drug targeting in live tissue in real-time and understand the factors that limit drug delivery is an important and exciting tool to target the progression of disease. A key element of this project’s approach will be to use novel 3D models that mimic cancer progression in living tissue, coupled with state-of-the-art imaging to separate this complex process into defined disease stages. The team has developed a methodology to map the fibrotic tumour landscape, through real-time imaging of (i) the proximity of cancer cells to the host blood supply, (ii) their location with regards to the tumour invasive borders and (iii) the surrounding tissue compartment.
Impact
Such versatile preclinical models are currently lacking and allow us to pinpoint which molecules are limiting anti-cancer targeting and tell us when intervention is appropriate. The combination therapy outlined in this current study along with patient biopsy data suggests that targeting susceptible patients (e.g. ‘high’ NID2 patients) with our new NID2 antibody may represent a novel and personalised approach. Tailoring anti-fibrotic co-targeting in this way could have long-term impact on pancreatic cancer control and management.