Dr Smaglo on the Evolution of RAS-Targeted Therapies for Pancreatic Cancer

In pancreatic cancer, [approximately] 80% to 90% of patients will have a mutation somewhere in KRAS. [These mutations are common enough] that it makes a lot of sense to chase down [these targeted therapies]. It's something where probably most patients, if not all patients, are going to have something that we can offer them if we can understand the status of their mutation."

Brandon G. Smaglo, MD, FACP, associate professor, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses how advances in understanding the biology of RAS mutations have helped catalyze the further development of novel RAS-targeted therapies for pancreatic cancer. Smaglo expanded upon these developments during Pancreatic Cancer Awareness Month, which occurs in November each year.

Smaglo notes that RAS mutations, particularly KRAS, can be found in the vast majority of patients with pancreatic cancer, making this a logical target in this malignancy. The role of RAS mutations in pancreatic cancer and other solid tumors has long been understood, but RAS mutations were historically considered "undruggable" targets, Smaglo explains. However, the prevalence and oncogenic role of RAS alterations in driving tumor progression and resistance have ensured that research efforts to develop RAS inhibitors have remained a priority, Smaglo explains.

Recent advances in molecular biology and drug development have enabled the identification of compounds capable of selectively targeting RAS mutations, which could eventually lead to additional treatment options, he says. Although work attempting to develop safe and efficacious RAS inhibitors has persisted, developments with novel agents in recent years have started to shift the needle, Smaglo says.

Data emerging from early-stage clinical trials evaluating these inhibitors has been encouraging, and the development of these agents could open the door for targeted therapies to play a larger role in the pancreatic cancer treatment paradigm, which has largely been a chemotherapy-only space, Smaglo concludes.