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Gene gating is the tethering of genes to nuclear pores to facilitate rapid nuclear export of transcripts. Scholz et al. show that gene gating of MYC increases nuclear export and overall expression of MYC transcripts in human colon cancer cells.
This Focus issue highlights current research into the unique biology of brain tumours and brain metastasis and how this research might improve therapy of these often devastating diseases.
Lin et al. and Lambo et al. report in-depth therapeutic screening and genomic profiling, respectively, of two types of aggressive paediatric central nervous system tumours, and both groups identify vulnerabilities of these tumours that might be exploited therapeutically.
Moya et al. have uncovered a non-cell autonomous, tumour suppressive mechanism of competition driven by the Hippo pathway effectors YAP and TAZ in peritumoural hepatocytes that limits liver cancer in mice.
Strickley, Messerschmidt et al. show that beta human papilloma virus (β-HPV) infection itself is not causal in cutaneous squamous cell carcinoma (SCC) development in the context of immunosuppression — instead, the loss of β-HPV-mediated T cell immunity promotes SCC.
Two papers report the discovery and preclinical analyses of two different covalent inhibitors of KRAS-G12C (AMG 510 and MRTX849) as well as the first data on the efficacy of these inhibitors in cancer patients.
Research by Chemi at al. highlights the potential of using pulmonary venous circulating tumour cells from patients with NSCLC, collected during tumour resection, to predict relapse and to explore mechanisms of early dissemination.
The microbiome is more than just bacteria. Now, the groups of Deepak Saxena and George Miller at New York University have linked alterations in the fungal component of the pancreatic microbiome, which activate the complement cascade, to pancreatic ductal adenocarcinoma growth and progression
Burr et al. report an evolutionarily conserved, tumour-intrinsic role for Polycomb repressive complex 2 (PRC2) in the epigenetic silencing of MHC class I antigen presentation pathway genes, illustrating that cancer cells can co-opt the immunomodulatory functions of PRC2 to evade immune surveillance.
Three studies show that synaptic interactions between neurons and glioma cells or cells of breast-cancer-to-brain metastases may promote tumour growth.
Morris IV et al. adapted a mouse model of human pancreatic ductal adenocarcinoma and found that p53-dependent metabolic changes restrain tumour progression through α-ketoglutarate accumulation and promotion of a premalignant cell fate.
In this Comment, the author, a cancer researcher and breast cancer survivor, discusses her experience as a patient with cancer and how it influenced her approach to research.
O’Connor et al. show that gliosis in the brain contributes to the development of central nervous system lymphomas (CNSLs) through the production of the chemokine CCL19 by astrocytes, which in turn promotes CNSL cell retention in the brain.
Using high-resolution proteomics to analyse clinical samples from patients with advanced melanoma, Harel et al. show that the metabolic state of melanoma is associated with changes in antigen presentation-related proteins and thereby with response to immunotherapies.
Ombrato et al. developed a fluorescent labelling system, which uses metastatic cells themselves to directly mark neighbouring cells in vivo and revealed the lung parenchyma to be a previously unrecognized component of the metastatic niche.
Rivadeneira et al. show that treatment of melanoma-bearing mice with the oncolytic Vaccinia virus recruits metabolically dysfunctional CD8+ T cells, which limits tumour regression. Vaccinia-mediated engineered expression of leptin in cancer cells improved responses through metabolic reprogramming of T cells.
In a study published in Cell, Dong et al. employ a genome-scale CRISPR screening approach to identify both known and previously uncharacterized regulators of CD8+ T cell activity, highlighting the utility of this approach for immunotherapeutic target discovery.
Zheng et al. have developed a phage-guided nanoparticle approach to modulate tumour-associated bacterial species and deliver chemotherapy for local release. This strategy was able to suppress tumour growth in mouse models of colorectal cancer.
Beyond the laboratory bench, cancer researchers will face big challenges during their careers. Nature Reviews Cancer has published two Viewpoint articles to highlight some of these wider issues.
Boettcher et al. show that missense mutations in the DNA-binding domain of TP53 lead to a dominant-negative effect in leukaemia, where mutant p53, instead of activating de novo transcriptional programmes, inhibits the wild-type protein, thereby driving clonal selection.
