Non-small-cell lung cancer articles from across Nature Portfolio

In this issue of Nature Metabolism, Brain, Vigil et al. show that NRF2-induced cystine uptake drives the formation of several cysteine–sugar metabolites. This process acts as a ‘sink’ for free cysteine and can lead to metabolic vulnerabilities and toxicity in NRF2-activated tumours.

Lymph node metastasis is critical in cancer staging and prognosis. Here, the authors use multimodal omics to explore the tumor microenvironment in non-small cell lung cancer (NSCLC) and identify FTH1-relevant cancer stemness, CXCL13+ T cell exhaustion and immune evasion contribute to lymph node metastasis of NSCLC.

In this issue of Nature Metabolism, Brain, Vigil et al. show that NRF2-induced cystine uptake drives the formation of several cysteine–sugar metabolites. This process acts as a ‘sink’ for free cysteine and can lead to metabolic vulnerabilities and toxicity in NRF2-activated tumours.

Spatial organization of the tumour microenvironment is instrumental for tumour progression or sensitivity to therapies. A new study reveals that tumour-associated highly glycolytic SLC2A1⁺ macrophages create metabolic borders that limit cytotoxic T cells and immunotherapeutic responses in lung cancer, providing a ‘metabolic–spatial’ framework for overcoming resistance to checkpoint blockade.

A study using single-cell 3D genome mapping reveals phenotypic convergence during mouse Kras-driven lung adenocarcinoma progression and prioritizes clinically actionable driver genes. This highlights the importance of cell-to-cell variation in chromatin architecture as a determinant of cancer evolution.