Metabolic rewiring in mutant Kras lung cancer

Emma M Kerr, Carla P Martins

Research output: Contribution to journalReview article

8 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages28-41
Number of pages14
JournalThe FEBS Journal
Volume285
Issue number1
DOIs
Publication statusPublished - 01 Jun 2018
Externally publishedYes

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Rats
Tumors
Lung Neoplasms
Cells
Oncogenes
Non-Small Cell Lung Carcinoma
Sarcoma
Neoplasms
Proteins
Survival Rate
Lung
Mutation
Adenocarcinoma of lung
Therapeutics
Synthetic Lethal Mutations

Cite this

Kerr, Emma M ; Martins, Carla P. / Metabolic rewiring in mutant Kras lung cancer. In: The FEBS Journal. 2018 ; Vol. 285, No. 1. pp. 28-41.
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Metabolic rewiring in mutant Kras lung cancer. / Kerr, Emma M; Martins, Carla P.

In: The FEBS Journal, Vol. 285, No. 1, 01.06.2018, p. 28-41.

Research output: Contribution to journalReview article

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AB - 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.

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