Pancreatic cancer has the lowest five-year survival rate of any cancer at 10%. It’s the fourth leading cause of cancer deaths in patients under 50. According to the American Cancer Society, about 62,000 Americans will be diagnosed with the disease this year.

Roughly 90% of pancreatic cancer tumors have a KRAS gene mutation. This gene makes a protein that changes healthy cells, causing them to behave like cancer. The natural, unchanged form of the gene is called KRAS wild-type, which accounts for about 10% of all pancreatic cancer cases. For decades, scientists and doctors have tried to block the activity of KRAS and other RAS proteins with little success.

A new study presented at the 2022 American Society of Clinical Oncology Annual Meeting hopes to use molecular testing to help find new targets for a cancer that was once considered “undruggable.”

Tomorrow at #ASCO22, Moffitt's @Todd_Knepper shares results from a comparative analysis looking at potential targets in KRAS-mutant and wild-type pancreatic adenocarcinoma. View abstract: https://t.co/5f5vwTxrL8 pic.twitter.com/J2YCH6Fvwl

— Moffitt Cancer Center (@MoffittNews) June 3, 2022

“Pancreatic cancer is one of the more challenging cancers to treat,” said Dr. Todd Knepper, associate member in the Department of Individualized Cancer Management at Moffitt Cancer Center. “Compared to some other types of cancer, we haven’t made significant progress in the development of targeted therapies for patients with pancreatic cancer. One potential reason for this stagnation is that roughly 90% of pancreatic cancer is characterized by a mutation in a gene called KRAS, which up until recently has been considered an undruggable target. In order to help bring new treatment options to patients and physicians, we were interested in learning more about the underlying differences between KRAS mutated and KRAS wild-type pancreatic cancer at the genomic and transcriptome level. Of particular interest are molecular alterations that can lead to new drug therapy options for patients, either now or in the future through the development of clinical trials."

“Prior studies, including have reported a greater frequency of potentially targetable gene fusions in the pancreatic cancers without KRAS-mutations, so we sought to verify and clarify these findings by partnering with a precision medicine technology company to help them analyze their data.”

Researchers looked at the molecular profiles of roughly 5,000 patients with pancreatic cancer to determine the differences in frequency of gene fusions and other clinically significant alterations.

Tumor tissue specimens are collected from patients, which then undergoes next generation sequencing capable of detecting gene fusions. While not all next generation sequencing testing platforms are optimized for the detection of gene fusions, utilizes RNA sequencing and allows researchers and physicians to gain a more complete view into the molecular landscape of each patient’s tumor.

“One of the things we found was a nearly fivefold increase in frequency in these potentially targetable gene fusions in patients with KRAS wild-type pancreatic cancer, in addition to an increased rate of detection of other clinically meaningful genomic findings,” said Knepper. “The use of molecular sequencing to identify what mutations are present in a patient’s tumor has become standard practice for patients with many advanced and metastatic malignancies. The findings from this study can help clinicians and patients with pancreatic cancer guide their decision-making around the likelihood of detecting potentially clinically meaningful alterations in their tumor, depending on KRAS-status.”

"The findings from this study can help clinicians and patients with pancreatic cancer guide their decision-making around the likelihood of detecting potentially clinically meaningful alterations in their tumor, depending on KRAS-status."

- Dr. Todd Knepper, Department of Individualized Cancer Management, @Todd_Knepper

Knepper says the goal for the study is to better understand the frequency of potentially targetable alterations in pancreatic cancer and identify the specific gene fusions that could potentially be targeted.

“This is one of the largest studies into the genomic landscape of KRAS wild-type pancreatic cancer,” said Knepper. “In the near-term, I think it would be a positive development if the results of this study helped to clarify the likelihood of detecting potentially targetable alterations in pancreatic cancer and helps get more patients matched to clinical trials. In the future, I hope that by expanding our understanding of pancreatic cancer, new safe and effective therapies can be developed to improve outcomes for people with cancer.”