GENETIC analysis of pancreatic tumours reveals characteristics of cells transitioning from normal, to pre-cancerous and cancerous pancreatic cells. Pancreatic cancer presents insidiously, has limited treatment options, and is often diagnosed at a late-stage when prognosis is poor, highlighted by the 5-year survival rate of 9%. Understanding the mechanisms underlying development of pancreatic cancer could help improve detection and treatment in the future.
To address these concerns, Li Ding, Department of Medicine, Department of Genetics, and McDonnell Genome Institute, Washington University, St Louis, Missouri, USA, and colleagues, performed an analysis of 83 pancreatic tumour samples of varying volume, donated from 31 patients at different stages of treatment, as part of the Human Tumor Atlas Network (HTAN).
The researchers assessed protein manufacturing and genetic profiles of each tumour sample. From their analysis, the team were able to map out two crucial transition points involved in pancreatic cancer development: the transition from normal pancreatic to pre-cancerous cells and from pre-cancerous to cancerous cells. Ding stated: “This marks the first time these transitions have been mapped out in such detail in human tumours.” Future work by the team will focus on identifying and mapping out the transition from non-metastatic to metastatic cancer.
Further to this, the team were able to identify a marker of potential chemotherapy resistance. They found that resistance to chemotherapy was associated with a three-fold increase in inflammatory cancer-associated fibroblasts encompassing the tumour. This finding is important given that the majority of pancreatic tumours become chemotherapy-resistant over time; therefore, developing therapeutics to target these fibroblasts could provide a solution to this problem. Moreover, the authors discovered a new signalling molecule combination that could be utilised to develop novel, effective checkpoint immunotherapies for pancreatic cancer.
These findings provide hope for the future in terms of identifying cells at the pre-cancerous stage to prevent progression to cancer, providing novel targets for cancer therapies, and helping overcome problems with chemotherapeutic drug resistance. Ding commented: “Our findings are jumping off points for the future development of new treatment strategies for this deadly cancer.”