Tearing down pancreatic cancer defences
Understanding role of CXCR2 in pancreatic cancer in search of new treatment options
3 June 2016
Scientists from AstraZeneca’s Oncology Innovative Medicines Unit, in collaboration with Dr. Jen Morton and Professor Owen Sansom of the Beatson Institute for Cancer Research in Glasgow, have shown how an experimental drug breaks down pancreatic cancers defences, allowing immune cells to attack the tumour.
The new study, published in Cancer Cell, discovered that a protein called CXCR2 acts as a guard for the tumour, controlling how the immune system responds to pancreatic cancer. The insights from this work are now being explored clinically with AZ13381758 (an analogue of AZD5069), AstraZeneca’s CXCR2 inhibitor, which has previously been studied in the clinic for COPD and asthma and is now being evaluated for squamous cell carcinoma of the head and neck.
This study highlights the value of the collaboration between CRUK and AstraZeneca in novel areas of biology that may bring benefits to patients.
Pancreatic cancer has a complex relationship with the immune system. In its early stages, the disease must evade the immune surveillance system, but once it has bypassed this initial attack, pancreatic cancer hijacks the immune system to aid its progression.
CXCR2 plays a pivotal role in regulating the recruitment of immune cells to sites of inflammation. It has been associated with poor outcomes for many tumour types and recent evidence has implicated it in pancreatic cancer. This collaboration studies the role of CXCR2 in tumour progression and assesses the value of CXCR2 inhibitors in this area of unmet need.
CXCR2 is located at the border between cancerous and healthy tissue. It regulates the movement of specialised immune cells that create a pro-tumour microenvironment and aids tumours evade attack from T-cells.
Deletion of CXCR2 was found to increase the amount of T-cells present in primary tumours and reduced the formation of distant metastases. Data showed that treatment with the CXCR2 inhibitor AZ13381758 enhanced the benefit of both chemotherapy and PD-1 antibodies.
The study findings were published in Cancer Cell in June 2016.