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News & Views |
A mitotic glue for shattered chromosomes
Two studies now shed light on how chromosomes that undergo catastrophic shattering are transmitted to daughter cells during cell division, thereby enabling them to be reassembled for the benefit of cancer cells.
- Yibo Xue
- & Daniel Durocher
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Review Article |
The neuroscience of cancer
This Review examines the interplay between the nervous system and tumours, from cancer initiation to progression and metastasis.
- Rebecca Mancusi
- & Michelle Monje
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Article |
Mitotic tethering enables inheritance of shattered micronuclear chromosomes
Chromothriptically produced pieces of a micronucleated chromosome are shown to be tethered together in mitosis by a protein complex consisting of MDC1, TOPBP1 and CIP2A, thus enabling their inheritance by a single daughter cell.
- Prasad Trivedi
- , Christopher D. Steele
- & Don W. Cleveland
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Article
| Open AccessCD4+ T cell-induced inflammatory cell death controls immune-evasive tumours
This article describes a mechanism through which CD4+ T cells can eradicate MHC-deficient tumours that escape direct CD8+ T cell targeting and thereby complement the activity of CD8+ T cells and natural killer cells to advance cancer immunotherapies.
- Bastian Kruse
- , Anthony C. Buzzai
- & Thomas Tüting
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News & Views |
Ultraviolet light shapes the evolution of precancerous cells
Much remains to be discovered about how premalignant cells become cancer cells. An analysis of the development of a type of human leukaemia implicates ultraviolet light in triggering a rare form of cancer.
- Elli Papaemmanuil
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Article
| Open AccessHeritable transcriptional defects from aberrations of nuclear architecture
Micronuclei, which are common features of nuclei in cancer cells, can generate heritable sources of transcriptional suppression, a finding that establishes an inherent relationship between chromosomal instability and variation in chromatin state and gene expression.
- Stamatis Papathanasiou
- , Nikos A. Mynhier
- & David Pellman
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Article
| Open AccessEpigenetic dysregulation from chromosomal transit in micronuclei
Missegregated chromosomes that are sequestrated in micronuclei are subject to changes in histone modifications leading to abnormalities in chromatin accessibility that remain long after the chromosomes have been reincorporated into the primary nucleus.
- Albert S. Agustinus
- , Duaa Al-Rawi
- & Samuel F. Bakhoum
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Article |
Tumour immune rejection triggered by activation of α2-adrenergic receptors
Agonists of α2-adrenergic receptors could substantially improve the clinical efficacy of cancer immunotherapy.
- Jingjing Zhu
- , Stefan Naulaerts
- & Benoit J. Van den Eynde
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Article
| Open AccessUltraviolet radiation shapes dendritic cell leukaemia transformation in the skin
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) arises from clonal (premalignant) haematopoietic precursors in the bone marrow, and BPDCN skin tumours first develop at sun-exposed anatomical sites and are distinguished by clonally expanded mutations induced by ultraviolet radiation.
- Gabriel K. Griffin
- , Christopher A. G. Booth
- & Andrew A. Lane
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News & Views |
Patterns of tumour transcriptional variability
The compilation and analysis of a compendium of single-cell RNA-sequencing studies across various cancers reveals recurring gene-expression programs that underpin tumour heterogeneity.
- Raymond W. S. Ng
- & Sydney M. Shaffer
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Article
| Open AccessIn situ tumour arrays reveal early environmental control of cancer immunity
Skin tumour array by microporation (STAMP) captures the dynamic relationships of spatial, cellular and molecular components of tumour rejection and has the potential to translate therapeutic concepts into successful clinical strategies.
- Guadalupe Ortiz-Muñoz
- , Markus Brown
- & Christine Moussion
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Article
| Open AccessPan-KRAS inhibitor disables oncogenic signalling and tumour growth
A non-covalent inhibitor that binds preferentially to the inactive state of KRAS while sparing NRAS and HRAS is reported, indicating that most KRAS oncoproteins cycle between an active state and an inactive state in cancer cells.
- Dongsung Kim
- , Lorenz Herdeis
- & Piro Lito
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Article |
Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours
A study identifies 41 consensus gene expression meta-programs that are coordinately upregulated in subpopulations of malignant cells across tumour types, providing a comprehensive picture of hallmarks of intratumour heterogeneity.
- Avishai Gavish
- , Michael Tyler
- & Itay Tirosh
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Article |
Tumour extracellular vesicles and particles induce liver metabolic dysfunction
Remote tumours cause liver dysfunction by releasing extracellular vesicles and particles containing palmitic acid, which induces TNF signalling in Kupffer cells, resulting in inflammation, fatty deposits and metabolic dysregulation, thus both reducing the efficacy and increasing the toxicity of chemotherapies.
- Gang Wang
- , Jianlong Li
- & David Lyden
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Outlook |
A fat-blocking drug could help to fight metastatic cancer
The antibody drug is moving closer to being tested in people with advanced stages of cancer.
- Elie Dolgin
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Article
| Open AccessERα-associated translocations underlie oncogene amplifications in breast cancer
An analysis of 780 breast cancer genomes shows that focal amplifications are frequently preceded by dicentric chromosome formation from inter-chromosomal translocations associated with oestrogen receptor binding, which leads to chromosome bridge formation and breakage, initiating the amplification process.
- Jake June-Koo Lee
- , Youngsook Lucy Jung
- & Peter J. Park
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Article
| Open AccessUridine-derived ribose fuels glucose-restricted pancreatic cancer
A metabolite screen of pancreatic cells shows that pancreatic cancer cells metabolize uridine-derived ribose via UPP1, supporting redox balance, survival and proliferation.
- Zeribe C. Nwosu
- , Matthew H. Ward
- & Costas A. Lyssiotis
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Article |
Lysine catabolism reprograms tumour immunity through histone crotonylation
Glioblastoma stem cells co-opt lysine uptake and degradation to shunt the production of crotonyl-CoA, remodelling the chromatin landscape to evade interferon-induced intrinsic effects on glioblastoma stem cell maintenance and extrinsic effects on immune response.
- Huairui Yuan
- , Xujia Wu
- & Jeremy N. Rich
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News |
Four challenges facing Biden’s nominee for NIH director
If confirmed, Monica Bertagnolli will grapple with congressional investigations, threats to funding, diversity issues and public distrust of science.
- Max Kozlov
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Career Q&A |
How my training helps me to address health disparities in multiple myeloma
Irene Ghobrial’s research on early detection of this type of bone-marrow cancer aims to improve patient outcomes, especially among African Americans.
- Frances Gatta
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News & Views |
Vaccine boosts T cells that target pancreatic tumours
Efforts to tackle pancreatic cancer by harnessing immune cells have had limited success. A clinical trial reports promising results from testing a personalized approach to boosting immune responses to such tumours.
- Amanda L. Huff
- & Neeha Zaidi
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News & Views |
Molecular basis for muscle loss that causes cachexia
Muscle loss during chronic disease is a life-threatening condition for which there is no effective treatment. The identification of an underlying molecular mechanism might offer new therapeutic targets.
- Laura Antonio-Herrera
- & Andreas Bergthaler
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Article
| Open AccessPersonalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer
A phase I clinical trial of an adjuvant personalized mRNA neoantigen vaccine, autogene cevumeran, in patients with pancreatic ductal carcinoma demonstrates that the vaccine can induce T cell activity that may correlate with delayed recurrence of disease.
- Luis A. Rojas
- , Zachary Sethna
- & Vinod P. Balachandran
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Article
| Open AccessPan-cancer whole-genome comparison of primary and metastatic solid tumours
The genomic differences between primary and metastatic tumours are assessed across 23 cancer types using pan-cancer whole-genome analysis.
- Francisco Martínez-Jiménez
- , Ali Movasati
- & Arne Van Hoeck
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Article
| Open AccessWidespread somatic L1 retrotransposition in normal colorectal epithelium
This study illustrates long interspersed nuclear element-1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime.
- Chang Hyun Nam
- , Jeonghwan Youk
- & Young Seok Ju
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Article |
EDA2R–NIK signalling promotes muscle atrophy linked to cancer cachexia
Gene expression analysis in muscle tissues showed upregulation of ectodysplasin A2 receptor in tumour-bearing mice and patients with cachectic cancer, and thus therapeutic targeting of relevant pathways may be beneficial in prevention of muscle loss.
- Sevval Nur Bilgic
- , Aylin Domaniku
- & Serkan Kir
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News & Views |
How thought itself can drive tumour growth
Tumour cells can form connections with neurons in the brain. Examination of a variety of types of evidence concerning human brain cancer sheds light on how these tumour–neuron interactions affect cognition and survival times.
- George M. Ibrahim
- & Michael D. Taylor
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Article
| Open AccessGlioblastoma remodelling of human neural circuits decreases survival
High-grade gliomas functionally remodel neural circuits in the human brain, promoting tumour progression and impairing cognition.
- Saritha Krishna
- , Abrar Choudhury
- & Shawn L. Hervey-Jumper
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News |
US cancer deaths are falling — but not fast enough
Models show that death rates must decline faster to meet Cancer Moonshot goals to cut deaths in half in 25 years.
- Heidi Ledford
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News & Views |
An unexpected timer for cell division
A serendipitous observation has revealed that cells make several versions of a key protein needed for cell division. The ratio of these protein isoforms influences how long division can be delayed when errors arise.
- Silke Hauf
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Article |
Alternative CDC20 translational isoforms tune mitotic arrest duration
Human cells modulate the duration of their mitotic arrest through the presence of conserved alternative CDC20 translational isoforms.
- Mary-Jane Tsang
- & Iain M. Cheeseman
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News |
Genetic map of Tasmanian devil cancers hints at their future evolution
Most detailed analysis yet pinpoints the contagious tumours’ origins.
- Gemma Conroy
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Article |
PI3Kβ controls immune evasion in PTEN-deficient breast tumours
A mouse model of invasive breast cancer in which Pten and Trp53 are simultaneously inactivated links PTEN loss with STAT3 activation and indicates that immune escape in PTEN-null tumours is mediated by PI3Kβ.
- Johann S. Bergholz
- , Qiwei Wang
- & Jean J. Zhao
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News & Views |
Enzyme lights dual fires to promote cancer
Tumours with certain cancer-driving mutations are difficult to treat. A discovery that one enzyme both controls proliferation and suppresses anticancer immune defences presages the exploration of new cancer-therapy strategies.
- Anghesom Ghebremedhin
- & Judith A. Varner
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News & Views |
Learning the metabolic language of cancer
The conversion of dietary sugar to the molecule lactate is a hallmark of many cancers. The discovery of a new binding partner of lactate provides insight into how cells link nutrient metabolism to the decision to divide.
- Minervo Perez
- & Jordan L. Meier
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Article |
Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA
Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.
- Christopher Abbosh
- , Alexander M. Frankell
- & Charles Swanton
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Article
| Open AccessGenomic–transcriptomic evolution in lung cancer and metastasis
Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.
- Carlos Martínez-Ruiz
- , James R. M. Black
- & Nicholas McGranahan
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Article
| Open AccessExtrachromosomal DNA in the cancerous transformation of Barrett’s oesophagus
An analysis of whole-genome sequencing data from patients with Barrett’s oesophagus or oesophageal ademocarcinoma shows that extrachromosomal DNA (ecDNA) is strongly associated with cancer progression, and that a wide range of oncogenes are amplified on ecDNAs.
- Jens Luebeck
- , Alvin Wei Tian Ng
- & Paul S. Mischel
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Article
| Open AccessAntibodies against endogenous retroviruses promote lung cancer immunotherapy
In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.
- Kevin W. Ng
- , Jesse Boumelha
- & George Kassiotis
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News & Views |
Epstein–Barr virus is an agent of genomic instability
A protein from Epstein–Barr virus called EBNA1 has been shown to bind to and break human chromosome 11, producing instability in the genome that might cause a predisposition to cancer.
- Lori Frappier
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News & Views |
Molecular portraits of lung cancer evolution
Assessing the genetic and cellular changes that underlie human lung cancer as it evolves could aid the development of treatments. The TRACERx project reports data from studies tracking the disease.
- Tikvah K. Hayes
- & Matthew Meyerson
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News & Views |
Extrachromosomal DNA appears before cancer forms
A type of circular DNA called extrachromosomal DNA was thought to be found exclusively in cancer. Its discovery in non-cancerous tissue suggests that it might have an early active role in malignant transformation.
- David H. Wang
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Article |
Chromosomal fragile site breakage by EBV-encoded EBNA1 at clustered repeats
Epstein–Barr Virus (EBV) nuclear antigen 1 is shown to induce breakage of a fragile site on chromosome 11 by binding to a cluster of EBV-like imperfect palindromic repeats.
- Julia Su Zhou Li
- , Ammal Abbasi
- & Don W. Cleveland
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Article
| Open AccessThe evolution of non-small cell lung cancer metastases in TRACERx
A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.
- Maise Al Bakir
- , Ariana Huebner
- & Charles Swanton
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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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