Prof Paul Timpson, head of the Invasion and Metastasis Lab, Professor Thomas Cox and Dr Brooke Pereira of the Garvan Institute of Medical Research were awarded funding from the Cancer Council to continue research into advancing treatment options for pancreatic cancer. The research will utilise advanced real time imaging and biosensor techniques to reveal the effect of treatments on pancreatic cancer.

Targeting pancreatic cancer (PC) and anti-fibrotic NID2 therapy and Gemcitabine/Abraxane chemotherapy treatment: stratifying PC therapy.

Pancreatic cancer is one of the most aggressive forms cancers, it is the third most common cancer in Australia with a low long term survival rate, mainly due to later stage diagnosis and resistance of the disease to treatment. The research teams of Prof Paul Timpson and Dr Brooke Pereira at the Garvan Institute have focused research on Pancreatic Ductal Adenocarcinoma (PDAC) which accounts for approximately 90% of pancreatic cancer cases. PDAC is a highly metastatic cancer that develops treatment resistance as it progresses, it is characterized by the formation of dense fibrous tissue that surrounds the cancer cells. This fibrosis acts as a barrier to effective treatment with current chemotherapy.

Prof Paul Timpson, Dr Brooke Pereira along with Professor Thomas Cox and their colleagues have shown that targeting the fibrotic tissue with anti-fibrotic therapy rendering the cancer cells more susceptible to treatment. Current research, published in the journal Science Advances, identified the glycoprotein nidogen-2 (NID2) molecule as a co-target for treatment in pancreatic cancer.

The team at the Garvan Institute have developed a way to map the tumour landscape and visualise the effects of treatments and progression of the disease in real time using 3D modelling that mimics the progression of cancer in living tissue and state of the art Intravital imaging, using these technologies and methods to investigate new treatment strategies for pancreatic cancer.

High NID2 expression has been associated with several solid malignancies including ovarian, breast and melanoma. Through analysis of APGI PDAC cohort along with real time imaging of mouse models, it was determined that high expression of NID2 was associated with poor survival in pancreatic cancer patients and was found to be predominantly expressed in cancer associated fibroblast cells. The research showed that depletion of NID2 in the tumour microenviroment decreased the matrix density, lead to smaller tumours and improved blood vessels, increasing the ability of chemotherapy drugs to further reduce the tumour and decrease fibrosis.

This work reinforces the importance of studies into the pretreatment of the tumour environment that could potentially lead to enhancing the efficacy of chemotherapy and ultimately improve survival outcomes for pancreatic cancer patients.

Further information on the work can be found here.