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Sökning: L773:2662 1347 > (2021)

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1.
  • Ferraro, Gino B., et al. (författare)
  • Fatty acid synthesis is required for breast cancer brain metastasis
  • 2021
  • Ingår i: Nature Cancer. - : Springer Science and Business Media LLC. - 2662-1347. ; 2:4, s. 414-428
  • Tidskriftsartikel (refereegranskat)abstract
    • Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2-positive breast cancer and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in the brain. We determine that this phenotype is an adaptation to decreased lipid availability in the brain relative to other tissues, resulting in site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase reduces human epidermal growth factor receptor 2-positive breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.
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2.
  • Helleday, T (författare)
  • Polθ inhibitors unchained
  • 2021
  • Ingår i: Nature cancer. - : Springer Science and Business Media LLC. - 2662-1347. ; 2:6, s. 581-583
  • Tidskriftsartikel (refereegranskat)
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3.
  • Lehtiö, Janne, et al. (författare)
  • Proteogenomics of non-small cell lung cancer reveals molecular subtypes associated with specific therapeutic targets and immune-evasion mechanisms
  • 2021
  • Ingår i: Nature Cancer. - : Springer Science and Business Media LLC. - 2662-1347. ; 2:11, s. 1224-1242
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite major advancements in lung cancer treatment, long-term survival is still rare and a deeper understanding of molecular phenotypes would allow the identification of specific cancer dependencies and immune-evasion mechanisms. Here we performed in-depth mass-spectrometry-based proteogenomic analysis of 141 tumors representing all major histologies of non-small cell lung cancer (NSCLC). We identified six distinct proteome subtypes with striking differences in immune cell composition and subtype-specific expression of immune checkpoints. Unexpectedly, high neoantigen burden was linked to global hypomethylation and complex neoantigens mapped to genomic regions, such as endogenous retroviral elements and introns, in immune-cold subtypes. Further, we linked immune evasion with LAG-3 via STK11 mutation-dependent HNF1A activation and FGL1 expression. Finally, we develop a data-independent acquisition mass-spectrometry-based NSCLC subtype classification method, validate it in an independent cohort of 208 NSCLC cases and demonstrate its clinical utility by analyzing an additional cohort of 84 late-stage NSCLC biopsy samples.
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  • Resultat 1-5 av 5

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