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| Open AccessPD-1-cis IL-2R agonism yields better effectors from stem-like CD8+ T cells
Binding of the PD1-IL2v immunocytokine to PD-1 and IL-2Rβγ on the same cell leads to an alternative differentiation of stem-like CD8+ T cells into better effectors rather than exhausted T cells in models of both chronic infection and cancer.
- Laura Codarri Deak
- , Valeria Nicolini
- & Pablo Umaña
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Article |
A mechanism for oxidative damage repair at gene regulatory elements
The nuclear mitotic apparatus protein NuMA helps to protect genes from oxidative damage by occupying regions around transcription start sites, binding DNA repair factors and promoting transcription following damage.
- Swagat Ray
- , Arwa A. Abugable
- & Sherif F. El-Khamisy
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Article |
A cellular hierarchy in melanoma uncouples growth and metastasis
A hierarchical model of melanoma tumour growth mirrors the cellular and molecular logic of cell-fate specification and differentiation of the underlying embryonic neural crest, and suggests that the ability to support growth and metastasis are limited to distinct pools of cells.
- Panagiotis Karras
- , Ignacio Bordeu
- & Jean-Christophe Marine
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Article |
Unified rhombic lip origins of group 3 and group 4 medulloblastoma
Multi-omic mapping shows that group 3 and group 4 medulloblastomas have a common, human-specific developmental origin in the cerebellar rhombic lip, providing a basis for their ambiguous molecular features and overlapping anatomical location, and for the difficulty of modelling these tumours in mice.
- Kyle S. Smith
- , Laure Bihannic
- & Paul A. Northcott
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News & Views |
The origins of medulloblastoma tumours in humans
How certain subgroups of a childhood brain tumour called a medulloblastoma arise has been unclear. Evidence now implicates a cell type found only in developing human brains as the originator of these tumours.
- Timothy N. Phoenix
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Article
| Open AccessAntibody targeting of E3 ubiquitin ligases for receptor degradation
Membrane-bound E3 ubiquitin ligases RNF43 and ZNRF3 are overexpressed in colorectal cancer, and can be repurposed using proteolysis-targeting antibodies (PROTABs) to selectively degrade cell-surface receptors in tumours.
- Hadir Marei
- , Wen-Ting K. Tsai
- & Felipe de Sousa e Melo
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Article |
Failure of human rhombic lip differentiation underlies medulloblastoma formation
Derailed differentiation of human-specific progenitors of the developing cerebellar rhombic lip is the cause of group 4 medulloblastoma, the most common childhood brain tumour.
- Liam D. Hendrikse
- , Parthiv Haldipur
- & Michael D. Taylor
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Outlook |
Researchers take on the challenge of prostate cancer
Fresh treatment options along with kinder and more accurate diagnostics promise to improve care.
- Richard Hodson
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Outlook |
Prostate cancer: highlights from research
Gut microbes drive treatment resistance, fresh hope for immunotherapy, and other studies and clinical trials.
- Annette Fenner
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Outlook |
Let’s talk about sex: tailoring prostate-cancer care for LGBT+ people
Personalizing cancer treatment doesn’t only mean matching a drug to molecular markers on a tumour — it should also take into account a person’s sexual identity, interests and wishes.
- Julianna Photopoulos
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Outlook |
Treat the mind, not just the body for prostate cancer
Urological oncologist Miguel Ángel Jiménez-Ríos explains how the psychological burden of the disease should change physicians’ approach to treatment and outreach.
- Laura Vargas-Parada
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Outlook |
How to improve the diagnosis of prostate cancer
Prostate-specific antigen is an established biomarker, but it is flawed. Research into alternatives is starting to get results, but will they reduce mortality?
- Benjamin Plackett
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Outlook |
The destructive power of PROTACs could tackle prostate cancer
Drugs that direct the body’s proteolytic capabilities towards cancer cells might overcome problems of treatment resistance.
- Simon Makin
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Outlook |
Racism and prostate cancer: a multilayered issue
Population-health researcher Joseph Ravenell explains the various origins of racial disparities in prostate cancer outcomes.
- Jyoti Madhusoodanan
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Outlook |
Does prostate-cancer treatment place a strain on the heart?
Hormonal therapy has helped many people with prostate cancer to live longer, fuller lives, but mounting evidence suggests that the drugs drive or exacerbate cardiovascular problems.
- Charlie Schmidt
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Outlook |
Metastatic prostate cancer: seeking a fresh chance of recovery
Advances in the ability to find and treat tumours that have spread around the body are changing the perception of what is possible for people with advanced disease.
- Charlie Schmidt
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Outlook |
Could immunotherapy finally break through in prostate cancer?
Despite success against other cancers, prostate tumours have so far resisted treatment with immunotherapy. But some researchers are persisting with the approach.
- Anthony King
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Outlook |
A better way to biopsy in prostate cancer
Imaging and advanced tissue sampling techniques could supplement or supersede conventional biopsies of the sensitive gland.
- Michael Eisenstein
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News Round-Up |
First exoplanet image, cancer deaths and pandemic preparation
The latest science news, in brief.
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Article
| Open AccessBrain-restricted mTOR inhibition with binary pharmacology
The combination of the brain-permeable mTOR inhibitor RapaLink-1 and the brain-impermeable FKBP12 ligand RapaBlock enable brain-specific inhibition of mTOR.
- Ziyang Zhang
- , Qiwen Fan
- & Kevan M. Shokat
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CDK11 regulates pre-mRNA splicing by phosphorylation of SF3B1
CDK11 associates with SF3B1 and phosphorylates threonine residues at the N terminus of SF3B1 during spliceosome activation, and the inhibition of CDK11 blocks the activation and leads to widespread intron retention and the accumulation of non-functional spliceosomes on pre-mRNAs and chromatin.
- Milan Hluchý
- , Pavla Gajdušková
- & Dalibor Blazek
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Columnar structure of human telomeric chromatin
Cryogenic electron microscopy analyses reveal a new, compact structure of telomeric chromatin, providing mechanistic insight into telomere maintenance and function.
- Aghil Soman
- , Sook Yi Wong
- & Lars Nordenskiöld
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News |
Billion-dollar US health agency gets new chief — but its direction remains in limbo
Biologist Renee Wegrzyn will take the reins at ARPA-H as lawmakers battle over its culture and priorities.
- Max Kozlov
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News |
Lost trees, booster benefits — the week in infographics
Nature highlights three key graphics from the week in science and research.
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Clinical Briefing |
Precision medicine improves outcomes in metastatic breast cancer
For breast cancers that have spread, a randomized phase II clinical trial shows that using genomic analysis to target therapies can improve outcomes, but only in people with a genetic alteration that has previously been associated with antitumour activity in clinical trials.
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Genomics to select treatment for patients with metastatic breast cancer
Targeted therapies matched to genomics improved progression-free survival when genomic alterations were classified as level I/II (according to ESCAT), and genomics should thus be driven by target actionability in patients with metastatic breast cancer.
- Fabrice Andre
- , Thomas Filleron
- & Ivan Bieche
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Article |
Methotrexate recognition by the human reduced folate carrier SLC19A1
Cryo-EM structures provide insight into how the antifolate methotrexate, a chemotherapy drug, is recognized by the reduced folate carrier.
- Nicholas J. Wright
- , Justin G. Fedor
- & Seok-Yong Lee
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Article
| Open AccessAfrican-specific molecular taxonomy of prostate cancer
A molecular taxonomy for prostate cancer reveals a subtype associated with copy-number loss found in African and European populations that predicts poor outcomes and two subtypes—one associated with high mutational noise and one with copy-number gain—specific to African populations.
- Weerachai Jaratlerdsiri
- , Jue Jiang
- & Vanessa M. Hayes
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Clinical Briefing |
Non-viral, precisely engineered immune cells tested in lymphoma
An improved approach has been developed for producing precisely designed immune cells called CAR T cells that recognize and kill cancer cells. CAR T cells generated in this way were safe and showed potential therapeutic effects in individuals with a relapsed or treatment-resistant form of the immune-cell cancer called B-cell non-Hodgkin’s lymphoma.
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News |
Almost half of cancer deaths are preventable
Data show that smoking, drinking alcohol and obesity are the biggest contributors to cancer worldwide.
- Giorgia Guglielmi
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Article
| Open AccessNon-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL
Non-viral CAR-T cells with gene-specific targeted integration are safe and effective in patients with lymphoma.
- Jiqin Zhang
- , Yongxian Hu
- & He Huang
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Article
| Open AccessRASA2 ablation in T cells boosts antigen sensitivity and long-term function
Genome-wide CRISPR screens, biochemical studies and animal models show that RASA2 has a key role in regulating T cell function and has potential as a genetic target for enhancing anti-tumour immunity.
- Julia Carnevale
- , Eric Shifrut
- & Alexander Marson
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Article
| Open AccessOrdered and deterministic cancer genome evolution after p53 loss
Malignant evolution enabled by p53 inactivation in mice proceeds through an ordered and predictable pattern of Trp53 loss of heterozygosity, accumulation of deletions, genome doubling and the emergence of gains and amplifications.
- Timour Baslan
- , John P. Morris IV
- & Scott W. Lowe
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Article
| Open AccessTruncated FGFR2 is a clinically actionable oncogene in multiple cancers
Truncation of exon 18 of FGFR2 (FGFR2ΔE18) is a potent driver mutation in mice and humans, and FGFR-targeted therapy should be considered for patients with cancer expressing stable FGFR2ΔE18 variants.
- Daniel Zingg
- , Jinhyuk Bhin
- & Jos Jonkers
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Nature Podcast |
Why low temperatures could help starve tumours of fuel
Cold exposure in mice activates brown fat to deny tumours glucose, and the future of extreme heatwaves.
- Benjamin Thompson
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Article
| Open AccessSpatially resolved clonal copy number alterations in benign and malignant tissue
Copy number variations inferred from spatial transcriptomics data in benign and malignant tissue reveal clonal architecture at the organ-wide level.
- Andrew Erickson
- , Mengxiao He
- & Joakim Lundeberg
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Research Highlight |
Cancer cells hijack nerve cells to storm through the brain
Cells of the deadly tumour glioblastoma hasten their advance by turning neurons to their advantage.
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Research Highlight |
Antibody–drug teamwork tames deadly metastatic brain tumours
Brain cancer that has its roots in the breast stops growing, and even shrinks, after a hybrid therapy.
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Article
| Open AccessBrown-fat-mediated tumour suppression by cold-altered global metabolism
Mild cold exposure activates a substantial amount of brown adipose tissue (BAT) in a patient with cancer, reducing tumour-associated glucose uptake, and activation of BAT in mice inhibits the growth of tumours by decreasing blood glucose and impeding glycolysis-based metabolism in cancer cells.
- Takahiro Seki
- , Yunlong Yang
- & Yihai Cao
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News & Views |
Akt protein boosts cancer metabolism through a two-pronged attack
Mutated forms of the protein Akt can be central drivers of cancer metabolism. A mechanism by which Akt promotes synthesis of the metabolic molecule coenzyme A broadens our understanding of the protein’s activity.
- Philipp Poeller
- & Almut Schulze
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Article
| Open AccessPI3K drives the de novo synthesis of coenzyme A from vitamin B5
The PI3K–PANK4 axis regulates coenzyme A synthesis, the abundance of acetyl-CoA, and CoA-dependent processes such as lipid metabolism, and these regulatory mechanisms coordinate cellular CoA supplies with the demands of hormone and growth-factor-driven or oncogene-driven metabolism and growth.
- Christian C. Dibble
- , Samuel A. Barritt
- & Alex Toker
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Article |
Deep whole-genome ctDNA chronology of treatment-resistant prostate cancer
Deep whole-genome sequencing of serial blood samples and matched metastatic tissue reveals that circulating tumour DNA profiling enables detailed study of treatment-driven subclone dynamics, epigenomics and genome-wide somatic evolution in metastatic human cancers.
- Cameron Herberts
- , Matti Annala
- & Alexander W. Wyatt
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Article
| Open AccessMechanisms of APOBEC3 mutagenesis in human cancer cells
Endogenous APOBEC3 deaminases generate prevalent mutational signatures in human cancer cells, and APOBEC3A is the main driver of these mutations.
- Mia Petljak
- , Alexandra Dananberg
- & John Maciejowski
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News |
COVID immunity, 3D nucleus — the week in infographics
Nature highlights three key graphics from the week in science and research.
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News Feature |
How gut bacteria could boost cancer treatments
Faecal transplants have helped some people to overcome resistance to powerful immunotherapies. Now dozens of trials are taking aim at the cancer–microbiome connection.
- Jeanne Erdmann
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Article |
Structure–function analysis of the SHOC2–MRAS–PP1C holophosphatase complex
- Jason J. Kwon
- , Behnoush Hajian
- & Andrew J. Aguirre
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News & Views |
Location in the nucleus foretells chromosome anomalies
A single-cell analysis suggests that the 3D location of chromosomes in the cell nucleus contributes to their likelihood of being involved in genomic rearrangements associated with cancer.
- Krishnendu Guin
- & Tom Misteli
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Review Article |
Inflammatory memory and tissue adaptation in sickness and in health
A Review on inflammatory memory in non-immune cells of different epithelia and neurons, and the potential mechanisms controlling these epigenetic memories and their implications in human health and disease.
- Shruti Naik
- & Elaine Fuchs
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News & Views |
Persister cells that survive chemotherapy are pinpointed
A close look at the cells that drive cancer growth after chemotherapy, and thereby contribute to fatal tumour progression, provides new insights into the identity of the cells that manage to survive treatment.
- Sumaiyah K. Rehman
- & Catherine A. O’Brien
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