Dr Cardin on Targeting KRAS in Pancreatic Cancer

Dana B Cardin, MD, MSCI, associate professor of medicine, Hematology and Oncology, Vanderbilt-Ingram Cancer Center, discusses the rationale for exploring KRAS as a therapeutic target in pancreatic cancer.

In an era where an increased understanding has been gained regarding the molecular profile of cancers and the genetic alterations that drive these malignancies, it has become possible to identify the gene alterations that most commonly occur in patients with a specific type of cancer, Cardin says. Within pancreatic cancer, KRAS mutations have been established as alterations responsible for driving the disease in a high proportion of patients, Cardin details.

Since KRAS alterations occur high in the signaling pathway, they can affect other downstream signals, Cardin expands. Studies investigating agents designed to target signals downstream of KRAS have not produced efficacious results, leading investigators to hypothesize that hitting the KRAS alteration directly is required for effective treatment, Cardin adds. However, developing KRAS-targeted agents has been a challenge in pancreatic cancer, she says.

Different types of agents, such as small molecule inhibitors, have been designed to target specific KRASmutations, Cardin continues, noting that there has been some activity noted with this research. KRAS G12C inhibitors have displayed antitumor activity in other malignancies; however, KRAS G12C mutations occur in approximately 1% to 3% of patients with pancreatic cancer, making this a small subset of this patient population, Cardin concludes.