Could Genetics Influence Pancreatic Cancer Survival Rates?

Study may help improve early cancer detection.

Improved survival rates for patients with pancreatic cancer were linked to a new set of genes discovered by researchers at the Translational Genomics Research Institute. The study also showed that detection of circulating tumor DNA (ctDNA) in the blood could provide an early indication of tumor recurrence.

The study used whole-exome sequencing, looking at the DNA protein-coding regions of 24 tumors, and targeted genomic analyses of 77 other tumors. The methods were used to evaluate mutations in chromatic-regulating genes MLL, MLL2, MLL3 and ARID1A in 20% of patients associated with improved survival.

Additionally, through liquid biopsy analysis, the study found that 43% of pancreatic cancer patients had ctDNA in their bloodstream at the time of diagnosis.

The study found that the presence of ctDNA was positively related to the recurrence of pancreatic cancer in patients and poor outcomes. Using the liquid biopsy worked to detect the recurrence of cancer 6.5 months earlier than using CT imaging.

“These observations provide predictors of outcomes in patients with pancreatic cancer and have implications for detection of tumor recurrence, and perhaps someday for early detection of the cancer,” said Dr. Daniel D. Von Hoff, TGen Distiguished Professor and Physician-in-Chief, Co-Director of TGen’s SU2C Pancreatic Cancer Dream Team, and Chief Scientific Officer at the Virginia G. Piper Cancer Center Clinical Trials at HonorHealth.

The pancreatic cancers observed in the study were stage II tumors from patients who underwent potentially curative surgery. Only 15 to 20% of patients are candidates for tumor resection. This is due to the fact that pancreatic cancer is difficult to detect and usually is not diagnosed until its late stages when surgery is no longer an option. The 5-year survival rate for those diagnosed with pancreatic cancer is less than 10%.

The study found that early detection of pancreatic cancer was possible through liquid biopsy analysis that focused on a few specific genetic alterations.

“We have identified MML genes as markers of improved prognosis for patients with pancreatic cancer,” said Dr. Von Hoff. “We have also shown that ctDNA in the blood of pancreatic cancer patients may provide a marker of earlier detection of recurrence of the disease.”

Further studies need to be done in order to evaluate more intensive therapies for patients without MLL mutations or with detectable ctDNA following surgical removal of their tumors, as well as interventional clinical trials.