Research led by the Dartmouth Geisel School of Medicine shows that epigenetic screening can predict pancreatic cancer prognosis and also whether tumors are likely to respond to therapy or not.
Pancreatic cancer has a poor prognosis, only 25% of people survive for one year after diagnosis. It is estimated to cause 48,220 deaths in the U.S. this year, accounting for 7.9% of all cancer deaths.
The most common type of pancreatic cancer is pancreatic ductal adenocarcinoma (90% cases) and treatment options are fairly limited. Most patients receive cytotoxic chemotherapy without the benefit of genetic or other prognostic testing to predict treatment response and many treatments fail.
In this study, Steven Leach, M.D., a professor at Dartmouth Geisel School of Medicine, and his team, as well as colleagues based at Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, tested genome-wide chromatin accessibility patterns for pancreatic tumors by creating an assay for transposase-accessible chromatin sequencing (ATAC-seq).
They tested the assay using tumor cells extracted from 54 human pancreatic tumors before the patients began treatment with chemotherapy. As described in the journal Nature Communications, they found an epigenetic signature of 1092 different markers on the chromatin that differed between patients who subsequently had disease free survival of less than one year compared with those who were disease-free for longer. Of these 1092 markers, they discovered that 723 are silenced in chemo-resistant tumors and are predictive of treatment response.
This kind of screening could help clinicians decide which pancreatic cancer patients are most likely to benefit from chemotherapy treatment and who is most likely to fall into the ‘non-responder’ group. Leach and colleagues think those in the latter group may benefit from epigenetic therapy, but this theory still needs to be validated.
“Whether adverse patterns of chromatin accessibility might assist in the selection of pancreatic ductal adenocarcinoma patients for epigenetic ‘reprogramming’ therapy remains to be determined,” write the authors.
“Nevertheless, we suggest that our ATAC-array technology… provides a simple and clinically achievable prediction of favorable vs unfavorable epigenetic states in this disease.”
There are already nine FDA-approved epigenetic drugs, many of which are designed to treat cancer, and more are more are being developed. While this is promising, it is still difficult to know which patients will benefit most from these therapies and more work is needed in this area.
“We currently appear to be at the dawn of a new era in which epigenetic reprogramming is poised to become increasingly relied upon to optimize therapeutic effectiveness in multiple tumor types,” says Leach.
“With this work, we have pioneered a precision epigenetic approach in pancreatic ductal adenocarcinoma, a treatment approach that is now ready to be translated into the clinic.”