Scientists have discovered two new subtypes of pancreatic cancer, as well as new types of stroma – dense surrounding tissue that can block drugs from reaching pancreatic tumours but that can also prevent the cancer from spreading.
The study, by UNC Lineberger Comprehensive Cancer Center researchers and collaborators, helps explain the conflicting role of the surrounding tissue known as stroma. In the study, the researchers revealed that based on molecular characteristics, there are two subtypes of pancreatic cancer stroma.
Researchers believe the findings could help doctors tailor treatments to individual patients, improving the results for treating a disease that has only a 7% 5-year survival rate.
Lead researcher Jen Jen Yeh, MD, said: “Right now, we still treat pancreatic cancers as one entity, while for some other cancers, we personalise treatment based on an individual patient’s tumour genetics or other characteristics.
“We believe these results will set the groundwork for future clinical trials, allow treatments to be assigned based on the subtypes, and guide the development of new therapies.”
The study has resulted in the most rigorously validated classification system for pancreatic ductal adenocarcinoma to date. Due to the complexity of pancreatic cancer and surrounding tissue, the researchers used a mathematical approach to separate the tissue. That approach, called blind source separation, allowed the researchers to separate normal and cancerous tissue and the stroma. The researchers then analysed 145 primary and 61 metastatic tumours, 17 cell lines, 46 normal pancreatic samples and 88 samples of normal, non-cancerous tissue taken from outside of the pancreas.
The researchers uncovered two subtypes of pancreatic stroma, which they called ‘normal’ and ‘activated’. The activated subtype resulted in worse survival outcomes.
“This study helps make sense of researchers’ conflicting findings about stroma – that it can either promote or be a barrier to tumour spread,” Yeh said. “We are seeing two distinct types of stroma in patients.”
Additionally, the researchers discovered two subtypes of pancreatic cancer tumours – ‘basal-like’ and ‘classical’. ‘Basal-like’ tumours were linked with worse outcomes for patients, with only 44% of patients living for 1 year after surgery, compared to a 70% survival rate for patients with the ‘classical’ subtype. However, basal-like tumours responded better to adjuvant therapy.
“If we know that your tumour is aggressive, then it may be important to treat your whole body first with neoadjuvant therapy, which is therapy given prior to surgery, as opposed to just trying to remove the tumour with surgery at the outset,” said Yeh.
“In addition, the basal-like subtype is very similar to basal breast and bladder cancers, which respond to therapies differently than other tumour subtypes, so we are very interested in seeing whether or not this is true for pancreatic cancer as well.”
Overall, the findings suggest that treatment decisions should be based on a patient’s stroma and tumour subtype.
The research was published in Nature Genetics.