Fewer than 7% of people with pancreatic cancer in the UK survive beyond five years, making it the deadliest common cancer. Surgery remains the only potentially curative option, yet only around 10% of patients are eligible for it, and as many as 70% receive no treatment at all. These statistics underline the urgent need for new and more effective therapies.
While immunotherapy has revolutionised treatment for many other cancers, it has shown limited success in pancreatic cancer, largely due to its unique, stroma-rich tumour microenvironment. Pancreatic tumours are characterised by extreme desmoplasia - a scarring response driven by cancer-associated fibroblasts (CAFs). These CAFs proliferate and secrete extracellular matrix, generating a dense, fibrotic stroma that makes it difficult for drugs and immune cells to penetrate. CAFs also secrete cytokines and growth factors to recruit and regulate immunosuppressive cells and to promote tumour invasion and metastasis.
The result is a physical and immunosuppressive barrier that prevents immune cells and drugs from reaching their targets and blunts the effectiveness of immunotherapies.
In collaboration with researchers from the Department of Oncology and the Nuffield Department of Surgical Sciences, Dr Wan’s fellowship will focus on developing a novel antibody-based immunotherapy designed to overcome CAF-mediated shielding and restore immune activity within pancreatic tumours, while sparing healthy tissues. To achieve this, the project prioritises the use of freshly resected pancreatic cancer biopsies to establish a translational platform for evaluating therapeutic efficacy and safety. Given the reciprocity between CAFs, their extracellular matrix, and the cancer cells, it is crucial to study them under conditions that mimic their natural state.
Dr Wan will also investigate combinational strategies with existing treatments, such as radiotherapy.
“Our antibodies are developed and tested directly using patient biopsy samples, keeping the research clinically relevant and enabling the most promising candidates to be accelerated towards clinical development. Importantly, this therapy will also work in combination with existing treatments such as chemotherapy and radiotherapy so that patients can gain substantial benefits with minimal additional interventions.” - Peter Wan, Pancreatic Cancer UK Fellow and Research Scientist at Department of Oncology, University of Oxford
Through this integrated approach, the project seeks to identify a lead antibody candidate that targets both cancer cells and the stromal barrier driving therapeutic resistance. By disrupting the immunosuppressive capacity of CAFs, this work could not only enhance anti-tumour immune responses, but also improve the overall effectiveness of existing treatments by remodelling the tumour microenvironment.
“I am extremely grateful to Pancreatic Cancer UK and all the donors for supporting me to conduct this exciting project. Developing better treatments for pancreatic cancer has long been my career ambition, as this is a disease where new options are urgently needed.”