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Open Access
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Article |
Noncoding translation mitigation
Combining genome-wide CRISPR screens with massively parallel analyses of human and random DNA sequences reveal a unified mechanism for the surveillance and evolution of translation products from annotated noncoding DNA.
- Jordan S. Kesner
- , Ziheng Chen
- & Xuebing Wu
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News & Views |
Air pollution’s role in the promotion of lung cancer
Air pollution is associated with the development of lung cancer. Analysis of clinical samples and mouse cancer models suggests that inflammation and a tumour-promotion process induced by polluted air are the major culprits.
- Allan Balmain
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News |
How air pollution causes lung cancer — without harming DNA
Studies in mice suggest that tumour growth is triggered by inflammation caused by tiny particles, rather than genetic mutations.
- Heidi Ledford
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Article |
Lung adenocarcinoma promotion by air pollutants
Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer
- William Hill
- , Emilia L. Lim
- & Charles Swanton
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News & Views |
A metabolic vulnerability of pancreatic cancer
Unusual metabolic pathways used by cancer cells offer possible targets for the development of clinical treatments. One such pathway, involving molecules called polyamines, has been found for pancreatic cancer.
- Daniel J. Puleston
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Article |
STING inhibits the reactivation of dormant metastasis in lung adenocarcinoma
STING signalling is activated in metastatic cancer cells that exit from an immune-evasive dormant state, blocking their progression and cancer relapse.
- Jing Hu
- , Francisco J. Sánchez-Rivera
- & Joan Massagué
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Article |
Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer
Pancreatic ductal adenocarcinoma cells show a specific dependency on ornithine aminotransferase-mediated ornithine synthesis from glutamine, providing an opportunity to develop targeted therapies with minimal toxicity for this cancer.
- Min-Sik Lee
- , Courtney Dennis
- & Nada Y. Kalaany
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News & Views |
Cancer cells remodel nuclear actin filaments to resist chemotherapy
Cancers that arise from epithelial cells often contain tumour cells that have acquired the characteristics of another cell type — a mesenchymal cell. A mouse model of skin cancer offers insights into why such cells resist treatment.
- Stephanie Panier
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Article
| Open AccessRHOJ controls EMT-associated resistance to chemotherapy
RHOJ regulates epithelial-to-mesenchymal-transition-associated resistance to chemotherapy by enhancing the response to replicative stress and activating the DNA damage response, enabling tumour cells to rapidly repair DNA lesions induced by chemotherapy.
- Maud Debaugnies
- , Sara Rodríguez-Acebes
- & Cédric Blanpain
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Article
| Open AccessRBFOX2 modulates a metastatic signature of alternative splicing in pancreatic cancer
Analysis of messenger RNA splicing in a large cohort of pancreatic ductal adenocarcinoma tumours identifies differential splicing correlating with disease progression, associated with the the splicing regulator RBFOX2.
- Amina Jbara
- , Kuan-Ting Lin
- & Rotem Karni
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Research Briefing |
Genome doubling perturbs DNA packing and promotes cancer development
Cells in which the whole genome has been doubled do not upscale protein synthesis to cope with the increase in DNA. Instead, a shortage of proteins that regulate the packing of DNA in the nucleus leads to poor segregation of DNA structures, which eventually contributes to the development of cancer.
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Clinical Briefing |
Inhibition of the protein menin shows early promise in leukaemia
Leukaemias characterized by the rearrangement of the gene KMT2A or mutation of the NPM1 gene depend on the protein menin. In a first-in-human trial, the menin inhibitor revumenib had minimal severe adverse effects and showed promising clinical activity in individuals with these types of leukaemia.
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Research Briefing |
Diversity of mitochondrial networks in lung cancer imaged
The structure and function of mitochondrial networks were analysed using a combination of approaches to generate detailed maps of these cellular organelles. This analysis revealed that the mitochondria in different subtypes of lung cancer show distinct functional and structural signatures.
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Article |
MEN1 mutations mediate clinical resistance to menin inhibition
Somatic mutations in MEN1 are identified in patients with leukaemia treated with a novel chromatin-targeting therapy, and the mechanism by which these mutations mediate therapeutic resistance is characterized.
- Florian Perner
- , Eytan M. Stein
- & Sheng F. Cai
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Article
| Open AccessThe menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia
Revumenib, a potent and selective oral inhibitor of the menin–KMT2A interaction, is associated with a low frequency of treatment-related adverse events and promising clinical activity in patients with relapsed or refractory acute leukaemia.
- Ghayas C. Issa
- , Ibrahim Aldoss
- & Eytan M. Stein
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Article
| Open AccessWhole-genome doubling drives oncogenic loss of chromatin segregation
Whole-genome doubling induces the loss of segregation of chromatin compartments, and can lead to tumour-promoting epigenetic and transcriptional modifications.
- Ruxandra A. Lambuta
- , Luca Nanni
- & Elisa Oricchio
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Article
| Open AccessThe dietary sweetener sucralose is a negative modulator of T cell-mediated responses
Consumption of high doses of the sweetener sucralose has immunomodulatory effects in mice, as a result of reduced T cell proliferation and differentiation.
- Fabio Zani
- , Julianna Blagih
- & Karen H. Vousden
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Article
| Open AccessSpatial mapping of mitochondrial networks and bioenergetics in lung cancer
A study describing an approach that combines imaging and profiling techniques to structurally and functionally analyse lung cancer in vivo, revealing heterogeneous mitochondrial networks and an association between bioenergetic phenotypes and mitochondrial organization and function.
- Mingqi Han
- , Eric A. Bushong
- & David B. Shackelford
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News |
Powerful AI models, and more — this week’s best science graphics
Three charts from the world of research, selected by Nature editors.
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Article |
Neoantigen-targeted CD8+ T cell responses with PD-1 blockade therapy
Effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8+ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time.
- Cristina Puig-Saus
- , Barbara Sennino
- & Antoni Ribas
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Article |
Co-opting signalling molecules enables logic-gated control of CAR T cells
Logic gating is used to develop a CAR T cell platform that is highly specific and allows the activity of T cells to be restricted to the encounter of two antigens, thus reducing on-target, off-tumour toxicity.
- Aidan M. Tousley
- , Maria Caterina Rotiroti
- & Robbie G. Majzner
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News |
Cancer will cost the world $25 trillion over next 30 years
And five types of cancer will account for almost half of the disease’s economic burden.
- Freda Kreier
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News & Views |
Bleb protrusions help cancer cells to cheat death
Processes that regulate cell death can rid the body of cancer cells. However, some of these cells have ways to thwart such processes, and one such death-defying mechanism has been found to rely on cellular protrusions called blebs.
- Michal Reichman-Fried
- & Erez Raz
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Article |
Blebs promote cell survival by assembling oncogenic signalling hubs
A study demonstrates that sustained membrane blebs in cancer cells recruit curvature-sensing septins that form plasma membrane-proximal signalling hubs that promote cancer cell survival.
- Andrew D. Weems
- , Erik S. Welf
- & Gaudenz Danuser
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News & Views |
Fatty acids prime the lung as a site for tumour spread
The mechanisms that enable the deadly spread of cancer are not fully understood. It emerges that tumours can signal to the lung to manipulate lipids and so prime the organ to support tumour cells that subsequently spread there.
- Laura V. Pinheiro
- & Kathryn E. Wellen
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Article
| Open AccessMicrobiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer
Indole-3-acetic acid (3-IAA), a tryptophan metabolite derived from the gut microbiota, is associated with a better response to chemotherapy in pancreatic ductal adenocarcinoma (PDAC), and dietary interventions could have a role in the treatment of PDAC.
- Joseph Tintelnot
- , Yang Xu
- & Nicola Gagliani
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News & Views |
A gut reaction can tune tumour fate during chemotherapy
The discovery that molecules produced by gut microorganisms can affect immune cells, and thus the success of chemotherapy for pancreatic cancer, points the way towards the use of nutritional interventions to improve outcomes.
- Le Li
- & Florencia McAllister
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Perspective |
CAR immune cells: design principles, resistance and the next generation
This Perspective reviews recent developments in the design and use of chimeric antigen receptors in treatments for cancers and other diseases.
- Louai Labanieh
- & Crystal L. Mackall
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Article |
TET2 guards against unchecked BATF3-induced CAR T cell expansion
Disruption of TET2 increases the antitumour efficacy of CAR T cells, but establishes an epigenetic state that is prone to hyperproliferation and accumulation of secondary mutations.
- Nayan Jain
- , Zeguo Zhao
- & Michel Sadelain
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Article
| Open AccessTelomere-to-mitochondria signalling by ZBP1 mediates replicative crisis
Dysfunctional telomeres activate innate immune responses through mitochondrial TERRA–ZBP1 complexes to eliminate cells that are destined for neoplastic transformation.
- Joe Nassour
- , Lucia Gutierrez Aguiar
- & Jan Karlseder
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Research Briefing |
Thrifty energy metabolism in solid tumours
The activity of two energy-producing metabolic pathways was recorded in different types of healthy tissue and solid-tumour tissue in mice. Comparisons of these measurements revealed that solid tumours make and use energy more slowly than do most healthy tissues, even though tumours grow and show cell division.
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Nature Podcast |
How mummies were prepared: Ancient Egyptian pots spill secrets
Analysis of substances uncovered in embalming workshop gives insight into the mummification process, and how CAR T therapies could turbocharge cancer treatments.
- Nick Petrić Howe
- & Benjamin Thompson
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Article
| Open AccessSingle-cell spatial immune landscapes of primary and metastatic brain tumours
Imaging mass cytometry of human brain tumours provides spatial information that, combined with existing transcriptomic data, reveals the existence of a cellular neighbourhood containing a rare macrophage population associated with prolonged survival.
- Elham Karimi
- , Miranda W. Yu
- & Logan A. Walsh
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Article
| Open AccessSingle-cell spatial landscapes of the lung tumour immune microenvironment
Using imaging mass cytometry, the tumour and immunological spatial landscapes of 416 lung adenocarcinomas are characterized, which, when combined with deep learning, can predict clinical outcomes with high accuracy.
- Mark Sorin
- , Morteza Rezanejad
- & Logan A. Walsh
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Article |
Slow TCA flux and ATP production in primary solid tumours but not metastases
As solid tumours develop, cancer cells shed energetically expensive tissue-specific functions, enabling uncontrolled growth despite a limited ability to produce ATP.
- Caroline R. Bartman
- , Daniel R. Weilandt
- & Joshua D. Rabinowitz
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News |
Where infectious diseases erupt, and more — this week’s best science graphics
Three charts from the world of research, selected by Nature editors.
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Book Review |
A crash course in biotech success — and failure
The unlikely discovery of a life-changing leukaemia drug uncovers harsh realities of profit and loss.
- Heidi Ledford
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News Feature |
The race to supercharge cancer-fighting T cells
With a slew of tools to trick out immune cells, researchers are expanding the repertoire of CAR-T therapies.
- Heidi Ledford
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News & Views |
Time of day shapes the success of a cancer treatment
Daily rhythms affect many aspects of mammalian biology. A discovery in mice that the activity of a key type of immune cell is shaped by such rhythms might have implications for clinical efforts to tackle cancer.
- Christian H. Gabriel
- & Achim Kramer
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Article |
Targeting TBK1 to overcome resistance to cancer immunotherapy
Targeting TBK1 is an effective strategy to overcome resistance to cancer immunotherapy.
- Yi Sun
- , Or-yam Revach
- & Russell W. Jenkins
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Article
| Open Accessγδ T cells are effectors of immunotherapy in cancers with HLA class I defects
γδ T cells contribute to the response to immune checkpoint blockade treatment in patients with HLA-class-I-negative DNA mismatch repair-deficient colon cancers. .
- Natasja L. de Vries
- , Joris van de Haar
- & Emile E. Voest
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News Feature |
Colonoscopies save lives. Why did a trial suggest they might not?
A major clinical study raised questions about one of the most celebrated cancer-screening procedures available, but a close look at the data tells a different story.
- Emily Sohn
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Article |
BRD8 maintains glioblastoma by epigenetic reprogramming of the p53 network
BRD8 is identified as a specific epigenetic vulnerability for glioblastomas that harbour wild-type p53.
- Xueqin Sun
- , Olaf Klingbeil
- & Alea A. Mills
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Outlook |
Could CAR-T-cell therapy offer hope to children with cancer?
The immunotherapy is beginning to show promise in solid tumours, but researchers want more dedicated research in young people.
- Elie Dolgin
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News & Views |
A refined use of mutations to guide immunotherapy decisions
Assessment of a tumour’s mutational profile offers a way of predicting a person’s response to anticancer therapies called immune-checkpoint inhibitors. It seems that such approaches might fall short for people who are not of European ancestry.
- Chao Cheng
- & Christopher I. Amos
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News |
Cancer treatments boosted by immune-cell hacking
Precision-controlled CAR-T-cell immunotherapies could be used to tackle a range of tumour types.
- Heidi Ledford
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Nature Index |
Challenging the high-dose paradigm for cancer drugs
The US Food and Drug Administration is looking at ways to lower approved doses to improve quality of life during chemotherapy.
- Marcus A. Banks
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News & Views |
Genetics and anatomy sculpt immune-cell partners of ovarian cancer
The therapeutic options available to treat ovarian cancer need improvement. Data that reveal the cellular, molecular and mutational landscape as such tumours grow and spread might aid efforts to develop new targeted therapies.
- Denarda Dangaj Laniti
- & George Coukos
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News & Views |
Heartbeat of brain tumours targeted
Analysis of an invasive brain cancer reveals that networks of tumour cells are linked to small groups of ‘pacemaker’ cells in which levels of calcium ions pulse periodically, driving a signal through the network that causes tumour growth.
- Benjamin Deneen
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