The Pancreatic Cancer UK Future Leaders Academy 2020 at the University of Cambridge 

Pancreatic cancer is a lethal disease with a dismal prognosis, with an overall 5-year survival rate of less than 9%. It is the fourth-leading cause of cancer related deaths in the United States, with an estimated 56,770 new cases and 45,750 deaths in 2019. In the UK, it is the fifth-leading cause of cancer-related mortality, the cause of 9263 deaths in 2016.

Tumour-stromal interactions have become a focus for potential novel therapeutic strategies in pancreatic cancer.

PDAC is characterized by its striking fibroinflammatory stroma, whose attendant dense, desmoplasia typically constitutes some 90% of tumour bulk. The stroma is generally thought to promote tumour growth by inhibiting the tumour immune system, providing growth factors and contributing to PDAC therapeutic refractoriness by impeding vascular perfusion and oxygenation, although recent evidence suggests that elements of the stroma have tumour-restraining properties.

Strategies targeting the stroma in PDAC have so far focused mainly on fibroblasts, specific components of the extracellular matrix such as hyaluronan, or angiogenesis. Although preclinical results were promising, in most cases this did not translate in the clinical setting. Pancreatic tumours are also resistant to immunotherapies that work in other cancers, such as PD-1/PD-L1 immune checkpoint blockade and anti-CTLA-4 antibodies. There is, therefore, a need for further research into the microenvironment of pancreatic tumours, to understand the interactions that influence pancreatic tumour development and growth, and to overcome resistance to treatment.

The overall vision for this Pancreatic Cancer UK Future Leaders Academy is an improved understanding of tumour-stromal and tumour-immune interactions in the hope of identifying therapeutic targets in PDAC.

                                                                                                                                                  Students in this Academy will study at the University of Cambridge. The Academy encompasses five research themes, with students being based at one of two departments, the Cancer Research UK Cambridge Institute and the Department of Biochemistry. The translational component of the research will be supported by the Cambridge Pancreatic Cancer Centre and the Hepatopancreatobiliary (HPB)  Surgical Unit at Addenbrooke’s Hospital.

Projects

Cancer Research UK Cambridge Institute

Genetic and epigenetic basis of fibroblast heterogeneity, plasticity and functions in pancreatic cancer
Biffi Group
Deadline: 22 November 2020

Interrogating tumour-associated mechanisms of immune escape in pancreatic cancer
Miller group
Deadline: 22 November 2020

Visualising ILC2/Treg interactions in the pancreas during pancreatic carcinogenesis 
Halim Group
Deadline: 22 November 2020

Counteracting immune evasion in DNA repair-deficient pancreatic cancers for immunotherapy 
Halim Group, in collaboration with Professor Ashok Venkitaraman and Mr. Siong-Seng 
Deadline: 22 November 2020

Department of Biochemistry

Deconstructing pancreatic adenocarcinoma
Professor Gerard Evan and Dr Trevor Littlewood 
Deadline: 7 December 2020