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<i>KRAS</i> is the most frequently mutated oncogene identified in human cancers. Despite the numerous efforts to develop effective specific inhibitors against <i>KRAS</i>, this molecule has remained “undruggable” for decades. The development of direct KRAS inhibitors, such as sotorasib, the first FDA-approved drug targeting <i>KRAS</i> G12C, or adagrasib, was made possible with the discovery of a small pocket in the binding switch II region of <i>KRAS</i> G12C. However, a new challenge is represented by the necessity to overcome resistance mechanisms to KRAS inhibitors. Another area to be explored is the potential role of co-mutations in the selection of the treatment strategy, particularly in the setting of immune checkpoint inhibitors. The aim of this review was to analyze the state-of-the-art of <i>KRAS</i> mutations in non-small-cell lung cancer by describing the biological structure of <i>KRAS</i> and exploring the clinical relevance of <i>KRAS</i> as a prognostic and predictive biomarker. We reviewed the different treatment approaches, focusing on the novel therapeutic strategies for the treatment of <i>KRAS</i>-mutant lung cancers.