Exploring Genetic Changes in Aggressive Pancreatic Cancer

Newswise — New Brunswick, N.J., October 2, 2023 – Small changes to healthy cells can sometimes lead to cancer. In almost every case of pancreatic cancer, one of those changes is a mutation in the gene KRAS, including pancreatic ductal adenocarcinoma (PDA), a highly aggressive type of pancreatic cancer. The genetic landscape of PDA based on KRAS status is not well studied. Investigators from Rutgers Cancer Institute of New Jersey and RWJBarnabas Health, the state’s leading cancer program and only National Cancer Institute-designated Comprehensive Cancer Center, investigated genomic alterations based on KRAS status to identify mutations in patients with KRAS wild type (WT).

Investigators include Matthew Pierre Deek, MD, radiation oncologist at Rutgers Cancer Institute and assistant professor of radiation oncology at Rutgers Robert Wood Johnson Medical School who is senior author, along with chief resident of radiation oncology Jongmyung Kim, MD, PhD. They share more about the work, which was presented orally at the 2023 American Society for Therapeutic Radiology and Oncology (ASTRO) Annual Meeting: https://astro2023.eventscribe.net/index.asp?sessionTarget=1246439

Why is this topic important to explore?

Pancreatic cancer remains a leading cause of morbidity and mortality in patients with cancer. A key player in this cancer is the KRAS mutation, found in over 90 percent of patients. Yet, we lack a thorough understanding of how the genetic makeup of pancreatic cancer relates to the presence or absence of KRAS mutations. Also, for patients who don't have this KRAS mutation, we don't understand what other genetic changes might be causing their cancer. In this study, we explore the genetic changes associated with KRAS status and their impact on patient outcomes.

Tell us about the work and what you and your colleagues found?

We used advanced genetic sequencing on patients with pancreatic cancer, analyzing more than 300 different human genes in more than 300 patients. We divided the genetic changes in these 300 genes into groups based on whether the patients had the KRAS mutation or not. What we discovered is that having the KRAS mutation is linked to a lower chance of survival, and patients with certain types of KRAS mutations are more likely to experience local failure after receiving radiotherapy. Additionally, we found several other genetic changes that could be responsible for causing pancreatic cancer in patients who do not have the KRAS mutation.

What does this mean for patients and what are next steps related to this work?

These findings may guide future clinical decision-making in the management of pancreatic cancer. Tailoring treatment plans according to a patient's KRAS status and targeting the specific genetic pathways we've identified might enhance patient outcomes in pancreatic cancer. Therefore, our next course of action involves confirming these findings through the design and execution of clinical trials, all with the aim of benefiting our patients.

Along with Drs. Kim and Deek, other authors on the work include Ritesh Kumar, MD, Lara Hathout. MD, FRCPC and Salma K. Jabbour, MD.