Abstract
The study of oncogenic RAS mutations has led to crucial discoveries regarding cancer molecular biology and behavior and has been integral in shaping the era of targeted cancer therapy. RAS mutations are one of the most common oncogenic drivers in human cancer, and intense efforts to find a clinically effective inhibitor are ongoing. Despite these efforts, targeting RAS mutations has remained elusive, so much so that some have termed oncogenic RAS mutations as "undruggable." In this review, we will summarize current understanding of RAS biology, explore strategies to inhibit RAS oncoproteins and its downstream effectors, and discuss recently described complexities that have shed new light on this pursuit.