Liu Y, Gao GF, Minna JD, et al. - The function of oncogenic RAS mutants (RAS ^MUT) is suppressed by wild type RAS (RAS ^WT) in laboratory models, and patients with RAS ^MUT cancers are found to have loss of RAS ^WT, which is termed loss of heterozygosity (LOH) for any RAS (LAR) or LAKR in the context of KRAS (LOH at KRAS), so researchers examined links between LAKR and cancer mortality among patients suffering from RAS ^MUT lung adenocarcinoma (LUAD). They also assessed for links between LAKR and the metabolic state of cancer cell lines and explored fatty acid synthase (FASN) inhibitors as potential treatment choices for RAS ^MUT LAKR, including combination approaches involving clinical KRAS ^G12C and FASN inhibitors. A median survival of 16 months and 30 months was seen in KRASMUT LAKR cases and in KRASMUT non-LAKR cases, respectively. Higher sensitivity to treatment with FASN inhibitors was evident in KRAS ^G12C LUAD cells with LAKR vs those without. Overall, LAKR in KRASMUT cancers was inferred to be a likely independent negative prognostic factor for patients experiencing KRASMUT LUAD. It was also shown to be predictive of the response to treatment with FASN inhibitors. It is justified to perform prospective testing of combination therapies including KRAS ^G12C and FASN inhibitors in patients with KRAS ^G12C LAKR.