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Research Highlight | December 14, 2020

Study reveals unique mutational pattern in patients with early-onset pancreatic cancer

Researchers from TFRI’s Enhanced Pancreatic Cancer Profiling for Individualized Care (EPPIC) team have made a new discovery about a worrying trend identified by researchers in recent years: the rise of pancreatic cancer in people age 55 and under.

In a study published in Clinical Cancer Research (October 2020), the research team led by Dr. Daniel Renouf, a medical oncologist and clinician-scientist at BC Cancer, revealed that patients with early-onset pancreatic cancer (EOPC) have a distinct mutational pattern in a gene called CDKN2A while also showing increased expression of the oncogenic transcription factor FOXC2. Combined, these two anomalies contribute to the early development of pancreatic cancer.

“Our study is unique in the way that it highlights novel molecular characteristics that may contribute to the development of EOPC,” said Dr. Erica Tsang, a former BC Cancer Medical Oncology Resident and the paper’s first author. “These findings advance the science of cancer and suggest there may be age-specific differences in the biology and development of pancreatic cancer.”

Understanding these age-related differences is important. According to Dr. Tsang, identifying the specific mutations that cause cancer can open new avenues for treatment that are more precise and effective.

“This finding is particularly important and may have significant implications, as ongoing trials are examining how to effectively target the CDKN2A mutation,” said Dr. Tsang. “This means that our results could begin to form the foundation for developing novel treatments for patients with EOPC.”

The importance of EPPIC

With a five-year survival rate of just nine per cent, pancreatic cancer is one of the most aggressive types of cancer. In recent years, many subtypes of this disease, including EOPC, have been on the rise.

To understand why this is happening and to find new ways to improve treatments the TFRI has been investing heavily in research groups like EPPIC, who are working to advance precision medicine approaches for this cancer.

As a pan-Canadian team, EPPIC researchers across the country work together to generate and analyze data from pancreatic cancer patients participating in clinical trials. According to Dr. Tsang, this concerted effort allowed the team to analyze a large quantity of samples, while also creating a collaborative framework that helped them make this important finding.

“We examined genomic data from Canadian patients in the PanGen and COMPASS clinical trials and worked closely with a team of clinicians and researchers in undertaking this research,” she said. “These pan-Canadian collaborations are essential in pooling our collective knowledge and expertise as we work towards the common goal of improving the treatment and quality of life of patients with pancreatic cancer.”

Study

Delving into Early Onset Pancreatic Ductal Adenocarcinoma: How Does Age Fit In?

Authors

Erica S. Tsang, James T. Topham, Joanna M. Karasinska, Michael K.C. Lee, Laura M. Williamson, Shehara Mendis , Robert E. Denroche , Gun Ho Jang, Steve E. Kalloger, Richard A. Moore, Andrew J. Mungall, Oliver Bathe, Patricia A. Tang, Faiyaz Notta, Julie M. Wilson , Janessa Laskin  Grainne M. O’Kane, Jennifer J. Knox, Rachel Goodwin , Jonathan M. Loree , Steven J. M. Jones, Marco A. Marra, Steven Gallinger, David F. Schaeffer, Daniel J. Renouf

Funding

The study was partially funded by a Terry Fox Translational Research Program grant to Enhanced Pancreatic Cancer Profiling for Individualized Care (EPPIC)