RAS is by far the most frequently mutated oncogene in human cancers, with ~1/3 of all human tumors harboring activating RAS mutations (Schubbert et al. 2007; Roberts and Der 2007). e gene product, Ras, is a small GTPase residing on the inner leaet of the plasma membrane, acting as a molecular switch by cycling between an inactive GDP-bound form and an active GTP-bound form. Binding of GTP causes conformational changes in the Ras protein that enable binding and activation of downstream eectors such as Raf and phosphoinositide 3-kinase (PI3K), through which Ras regulates many key aspects of cell physiology, including growth, proliferation, and survival, among others (Cox and Der 2010).