In the Journals

Gene mutations may match patients to pancreatic cancer treatments

Researchers from the University of Pittsburg Medical Center have found specific genetic mutations that revealed which pancreatic cancer tumors could be susceptible to existing chemotherapy drugs, according to an analysis published in Gastroenterology.

Nathan Bahary, MD, PhD, an oncologist at UPMC Hillman Cancer Center, in Pittsburgh, said in a press release that their findings could help match patients to treatments.

“People have been looking for such markers for a long time, and our study shows that it's possible to break pancreatic cancer patients into different treatment buckets,” he said in the release.

Bahary and colleagues performed a targeted genomic profile analysis of 3,594 pancreatic ducal adenocarcinoma samples taken from an international cohort provided by their partners at Foundation Medicine. They also used capture-based targeted genomic profiling in approximately 315 cancer-associated genes and intron regions of 28 genes that are rearranged in cancer cells. Researchers assessed tumor mutation burden and microsatellite instability.

In the 12% of samples that did not include a mutation to KRAS — a common mutation found in pancreatic cancer — investigators found alterations in genes whose products are in the mitogen-activated protein kinase signaling pathway and are drug targets (actionable targets; n = 132; 4%), as well as gene fusions (n = 51), gene amplifications (n = 35), genes with missense mutations (n = 30) and genes that contain deletions (n = 16).

Cancer Cell DNA
Researchers indentifed gene mutations that might help match patients to pancreatic cancer treatments.
Source: Adobe Stock

Bahary and colleagues wrote that many of these endcode proteins in receptor tyrosine kinase, RAS, or mitogen-activated protein kinase signaling pathways which could confer susceptibility to current anticancer therapy.

Additionally, researchers found that alterations in FGF23, CCND2, PIK3CA, FGF6 were more commonly found in intraductal mucinous neoplasm-associated pancreatic cancers. These alterations could also be used as biomarkers for early detection.

Lead author Aatur D. Singhi, MD, PhD, a surgical pathologist at UPMC and assistant professor of pathology at the University of Pittsburgh, said the goal is to make molecular profiling of patients the standard of care in pancreatic cancer.

“Every pancreatic cancer is different and performing molecular profiling of each patient's tumor could help determine the best treatment options,” Singh said in the release. “Rather than blindly giving patients the same chemotherapy, we want to tailor a patient's chemo to their tumor type. A one-size-fits-all approach isn't going to work.” – by Alex Young

Disclosures: Bahary reports no relevant financial disclosures. Singhi reports receiving honoraria from Foundation Medicine. Please see the full study for all other authors’ relevant financial disclosures.

Researchers from the University of Pittsburg Medical Center have found specific genetic mutations that revealed which pancreatic cancer tumors could be susceptible to existing chemotherapy drugs, according to an analysis published in Gastroenterology.

Nathan Bahary, MD, PhD, an oncologist at UPMC Hillman Cancer Center, in Pittsburgh, said in a press release that their findings could help match patients to treatments.

“People have been looking for such markers for a long time, and our study shows that it's possible to break pancreatic cancer patients into different treatment buckets,” he said in the release.

Bahary and colleagues performed a targeted genomic profile analysis of 3,594 pancreatic ducal adenocarcinoma samples taken from an international cohort provided by their partners at Foundation Medicine. They also used capture-based targeted genomic profiling in approximately 315 cancer-associated genes and intron regions of 28 genes that are rearranged in cancer cells. Researchers assessed tumor mutation burden and microsatellite instability.

In the 12% of samples that did not include a mutation to KRAS — a common mutation found in pancreatic cancer — investigators found alterations in genes whose products are in the mitogen-activated protein kinase signaling pathway and are drug targets (actionable targets; n = 132; 4%), as well as gene fusions (n = 51), gene amplifications (n = 35), genes with missense mutations (n = 30) and genes that contain deletions (n = 16).

Cancer Cell DNA
Researchers indentifed gene mutations that might help match patients to pancreatic cancer treatments.
Source: Adobe Stock

Bahary and colleagues wrote that many of these endcode proteins in receptor tyrosine kinase, RAS, or mitogen-activated protein kinase signaling pathways which could confer susceptibility to current anticancer therapy.

Additionally, researchers found that alterations in FGF23, CCND2, PIK3CA, FGF6 were more commonly found in intraductal mucinous neoplasm-associated pancreatic cancers. These alterations could also be used as biomarkers for early detection.

Lead author Aatur D. Singhi, MD, PhD, a surgical pathologist at UPMC and assistant professor of pathology at the University of Pittsburgh, said the goal is to make molecular profiling of patients the standard of care in pancreatic cancer.

“Every pancreatic cancer is different and performing molecular profiling of each patient's tumor could help determine the best treatment options,” Singh said in the release. “Rather than blindly giving patients the same chemotherapy, we want to tailor a patient's chemo to their tumor type. A one-size-fits-all approach isn't going to work.” – by Alex Young

Disclosures: Bahary reports no relevant financial disclosures. Singhi reports receiving honoraria from Foundation Medicine. Please see the full study for all other authors’ relevant financial disclosures.