Mutated RAS: Targeting the "Untargetable" with T-cells

The RAS family of proteins are at the apex of several pathways implicated in a multitude of epithelial cancers, but have remained stubbornly resistant to the wave of targeted small molecules and antibodies that have revolutionized clinical oncology. KRAS, the most commonly mutated of the isoforms, represents an attractive target for treatment given its ubiquity, central role as a driver mutation and association with poor prognosis. This review is a comprehensive summary of the existing approaches to targeting KRAS spanning small molecule inhibitors, cancer vaccines, and with a focus on trials in adoptive cell therapy. Here we explain how the limitations of existing drugs and non-specific immune-based therapies are circumvented with techniques in modern immunotherapy. The successes outlined represent the most promising path to finally targeting the prototypical "undruggable" RAS oncogene family.