Pancreatic cancer has one of the worst outcomes of any cancer, with a 5-year survival of less than 5%. It persists as the 4th leading cause of cancer death in our society, and, due to lack of progress, will soon be the 2nd. Taking on this challenge, Precision-Panc is a UK wide
therapeutic development platform based at the University of Glasgow’s Wolfson Wohl Cancer Research Centre (WWCRC) led by Professor Andrew Biankin. Leveraging on the success of previous international endeavours including the Australian Pancreatic Cancer Genome Initiative, and the International Cancer Genome Consortium, the core of Precision-Panc serves to integrate and align translational research with therapeutic development. We want to bring novel drugs to patients and learn as much as possible in the process to understand pancreatic cancer better, and ultimately improve patient survival.
Traditional therapeutic strategies have failed to impact on survival as only a small proportion of patients benefit from any single treatment. A precision medicine approach aims to use targeted next-generation genomic sequencing of tumour biopsies, to better guide patients to therapies, while providing a wealth of new information about the genomic features of pancreatic cancer. While clinical trials are vital in developing and improving treatments, only a tiny proportion of all patients enrol in cancer clinical trials each year. This approach is designed to address this problem and increase recruitment through a patient-centric approach. Precision-Panc will “Find the Optimal Trial for each Participant”.
Like any big scientific endeavour, it takes a team of committed individuals to recruit participants onto the Precision-Panc platform and help them progress on their journey. Patient’s that have been referred with a potential diagnosis of pancreatic cancer from across the West of Scotland are discussed every week at a Multidisciplinary Meeting (MDM) at Glasgow Royal Infirmary attended by everyone involved in the patient pathway including
surgeons, oncologists, radiologists, pathologists, gastroenterologists, specialist nurses, and pancreatic cancer researchers. This meeting ensures every patient has the benefit of a
variety of experts contributing to their care.
Our work centres around finding the right trial for the patient. The essential concept is that when a patient first comes to a hospital clinic with suspected pancreatic cancer, we have a conversation with them up-front on the day following the MDM. A member of the Precision- Panc team explains that a clinical trial may potentially be the best option for them, so that the opportunity is identified early to save time, as well as avoiding the need to repeat tests later. Therefore, we gather all the things we need as part of the routine pathway of care. The only difference being that some additional material is taken during the biopsy of the tumour. This sample is transferred to the NHS pathology laboratory at the Queen Elizabeth University Hospital where the pathology team reviews it, confirms the diagnosis of pancreatic cancer, assures the quality of the specimen, and extracts the DNA required for analysis.
Finally, the sample is sent to The Glasgow Precision Oncology Laboratory at the WWCRC were we perform clinically relevant genomic assays and generate a report for clinicians and patients that reports the key genomic features of the patient’s tumours allowing them both to make an informed decisions based on the available options including entry into one of the PRIMUS (Pancreatic CanceR Individualised Multi-arm Umbrella Study) trials.
In alignment with the direction of the NHS, we hope to enable every patient with pancreatic cancer to have their cancer genome examined, potentially unlocking access to clinical trials. Challenges of therapeutic development in pancreatic cancer One of the challenges that we face both in pancreatic cancer and many other cancer types is that most of the drugs do not work in the majority of patients. This is a core aspect of Precision-Panc, getting the right treatment to the right patients at the right time for the right cost and the right outcome. If we have samples of cancer and blood from these patients, we can dig deep into understanding the molecular features of the cancer, informing us why something worked and why something didn’t so that we can continue to learn, and improve, so as to deliver the most appropriate treatment to individual patients.
Negotiating the nihilism associated with the treatment of pancreatic cancer is a constant challenge, however, the treatment landscape for pancreatic cancer is rapidly evolving. Central to the success of this strategy is making patients, and doctors aware of the trials
available and for them to be seen as realistic treatment options. Due to the aggressive nature of pancreatic cancer, speed is vital at every step. Rapid fast-tracking referral of patients with suspicious symptoms or worrisome imaging tests followed by rapid processing time on molecular assays is vital in order to provide data in a clinically meaningful timeframe to enable treatment decisions. The team has developed a genomic assay for which results can be fed back to the MDM within 7 days of receipt of samples. Prior to initiating a precision oncology strategy the reporting time for diagnostic pancreatic biopsies alone, which are incredibly challenging to interpret, could often exceed this target.
Therefore, the infrastructure provided by Precision-Panc has already enhanced the delivery of patient care. Collaboration across multiple clinical sites in the UK is necessary to impact this disease. The decision to use formalin-fixed, paraffin-embedded tumour tissue, although more challenging to analyse compared to frozen tissue, enables us to recruit many more centres and patients to the Precision-Panc platform. Standardisation and reproducibility are
therefore vital across these sites to ensure validity of the results particularly when such sensitive assays are used such that even variation in the solution that the sample is stored in could alter results.
While the current challenge of Precision-Panc will be to spread the word to newly diagnosed patients and clinicians alike, ongoing funding and self-sustainability will be key to long term success. This will be also be vital to the integration of multi-pronged therapeutic strategies including immunotherapy and the analysis of increasingly complex datasets.
Overall, Precision-Panc is an extremely exciting initiative with real potential to improve outcomes for patients with pancreatic cancer through a precision medicine approach. This once again demonstrates the world leading position of Scotland and the UK in this area of research and clinical implementation.