3 years ago

Metabolic rewiring in mutant Kras lung cancer

Metabolic rewiring in mutant Kras lung cancer
Carla P. Martins, Emma M. Kerr
Lung cancer is the leading cause of cancer-related death worldwide, reflecting an unfortunate combination of very high prevalence and low survival rates, as most cases are diagnosed at advanced stages when treatment efficacy is limited. Lung cancer comprises several disease groups with non small cell lung cancer (NSCLC) accounting for ~ 85% of cases and lung adenocarcinoma being its most frequent histological subtype. Mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) affect ~ 30% of lung adenocarcinomas but unlike other commonly altered proteins (EGFR and ALK, affected in ~ 14% and 7% of cases respectively), mutant KRAS remains untargetable. Therapeutic strategies that rely instead on the inhibition of mutant KRAS functional output or the targeting of mutant KRAS cellular dependencies (i.e. synthetic lethality) are an appealing alternative approach. Recent studies focused on the metabolic properties of mutant KRAS lung tumours have uncovered unique metabolic features that can potentially be exploited therapeutically. We review these findings here with a particular focus on in vivo, physiologic, mutant KRAS activity. Lung cancer is the leading cause of cancer-related death worldwide. Mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) are common drivers of lung adenocarcinoma but remain a challenging therapeutic target. Recent studies demonstrated that mutant KRAS lung tumours exhibit unique metabolic features and dependencies, which can potentially be exploited to target these aggressive cancers. This review discusses these findings and their potential therapeutic implications.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/febs.14125

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