Oncology articles within Nature Communications

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  • Article
    | Open Access

    Tumour microenvironment actively contributes to drug resistance in clinical oncology. Here, the authors show that genotoxic stress induces senescence in human stromal cells, which in turn secrete serine protease inhibitor Kazal type 1 (SPINK1) and promote acquired resistance of cancer cells via EGFR-mediated paracrine signaling.

    • Fei Chen
    • , Qilai Long
    •  & Yu Sun

  • Article
    | Open Access

    In pancreatic neuroendocrine tumors (PanNETs) ATRX, DAXX, and MEN1 are commonly mutated (A-D-M mutant PanNETs). Here, the authors find in a cohort of PanNETS 58% are A-D-M mutant PanNETs, with a worse clinical outcome and differences in gene expression and methylation compared to A-D-M wild type cases- these gene expression differences suggest that A-D-M mutant PanNETs potentially originate from a cell type similar to alpha cells.

    • Chang S. Chan
    • , Saurabh V. Laddha
    •  & Laura H. Tang

  • Article
    | Open Access

    Chr3q26 rearrangements cause overexpression of EVI1 and associate with myeloid neoplasms, but the mechanism behind this association is unclear. Here, using a novel mouse model they show that EVI1 causes premalignant myeloid expansion with suppression of other lineages through upregulation of Spi1/PU.1.

    • Edward Ayoub
    • , Michael P. Wilson
    •  & Archibald S. Perkins

  • Article
    | Open Access

    In growth and development genomic imprinting is important in regulating gene expression. Here, the authors study loss of imprinting (LOI) in cancer, developing a mixture model to detect monoallelically expressed loci without genotyping data - applying this novel methodology to TCGA breast cancer data they find massive deregulation of imprinting.

    • Tine Goovaerts
    • , Sandra Steyaert
    •  & Tim De Meyer

  • Article
    | Open Access

    The driver mutations for the two main molecular subgroups of diffuse large B-cell lymphoma (DLBCL) are poorly defined. Here, an integrative genomics analysis identifies 3′ UTR NFKBIZ mutations within the activated B-cell DLBCL subgroup and small FCGR2B amplifications in the germinal centre B-cell DLBCL subgroup.

    • Sarah E. Arthur
    • , Aixiang Jiang
    •  & Ryan D. Morin

  • Article
    | Open Access

    Several challenges are involved in direct targeting of mutant p53, while targeting altered fitness of cells with loss of wild type p53 is an alternative approach. Here they identify niclosamide to be selectively toxic to p53 deficient cells through a previously unknown mitochondrial uncoupling mechanism.

    • R. Kumar
    • , L. Coronel
    •  & C. F. Cheok

  • Article
    | Open Access

    Acquired resistance is a major problem in cancer immunotherapy. Here the authors report a study of two patients with Merkel cell carcinoma under immunotherapy treatment who develop resistance after deep responses for >1 year and identified a novel mechanism of acquired, gene-specific transcriptional suppression of HLAs.

    • K. G. Paulson
    • , V. Voillet
    •  & A. G. Chapuis

  • Article
    | Open Access

    Fluorescent tracers are being tested in clinical trials to improve detection of tumor margins, but procedures are not standardised. Here, the authors develop an analytical framework that is compatible with the workflow in the operating theatre, and show that it leads to an 88% increase in intraoperative detection of tumor margins in patients with breast cancer.

    • Marjory Koller
    • , Si-Qi Qiu
    •  & Gooitzen M. van Dam

  • Article
    | Open Access

    Small cell lung cancer (SCLC) patients frequently relapse and become resistant to chemotherapy. Here, the authors analyse the genomic and transcriptomic landscape of primary and relapsed SCLC patients as well as in vitro models, and discover that activation of WNT signalling can drive chemotherapy resistance.

    • Alex H. Wagner
    • , Siddhartha Devarakonda
    •  & Ramaswamy Govindan

  • Article
    | Open Access

    Multiple myeloma is a cancer of the plasma cells, and the complete aetiology of the disease is still unclear. Here the authors perform an additional GWAS analysis followed by a meta-analysis with existing GWAS and replication genotyping and identify 6 novel risk loci and utilise gene expression, epigenetic profiling and in situ Hi-C data to further our understanding of MM susceptibility.

    • Molly Went
    • , Amit Sud
    •  & Stephen N. Thibodeau

  • Article
    | Open Access

    Hofvander and colleagues compare the patterns of clonal evolution in different pathogenetic subgroups of sarcoma. They show that sarcomas driven by gene fusion or amplification display few additional changes over time, whereas sarcomas with complex karyotypes show a gradual increase of nucleotide- and chromosome-level mutations.

    • Jakob Hofvander
    • , Björn Viklund
    •  & Fredrik Mertens

  • Article
    | Open Access

    Triple-negative breast cancer is highly heterogeneous and aggressive. Here, the authors utilise single-cell RNA sequencing to investigate this heterogeneity, and discover a subpopulation of cells associated with metastasis and treatment resistance signatures, and linked to long term survival outcomes.

    • Mihriban Karaayvaz
    • , Simona Cristea
    •  & Leif W. Ellisen

  • Article
    | Open Access

    The c-MYC oncoprotein has many targets whose actions are not fully understood including TFAP4/AP4. Here, the authors show in a mouse model of inherited colorectal cancer that deletion of AP4 decreased the frequency of c-MYC-driven intestinal adenomas, and reveal Ap4 as a mediator of adenoma initiation and regulator of colonic and intestinal stem cell and Paneth cell homeostasis.

    • Stephanie Jaeckel
    • , Markus Kaller
    •  & Heiko Hermeking

  • Article
    | Open Access

    The Hippo pathway is frequently dysregulated in cancer. Here, the authors identify NUAK2 as negative regulator of the Hippo pathway from a siRNA kinome screen and show that NUAK2 promotes YAP/TAZ nuclear localisation while NUAK2 is a transcriptional target of YAP/TAZ, thus providing a feed forward loop to promote tumorigenesis.

    • Mandeep K. Gill
    • , Tania Christova
    •  & Liliana Attisano

  • Perspective
    | Open Access

    Understanding the contributions of extrinsic and intrinsic factors on cancer risk is fundamental in determining the intervention and prevention strategies to tackle cancer. Here the authors provide a review of the different factors impacting cancer risk and discuss the limitations of different approaches in evaluating the relative contributions of these factors.

    • Song Wu
    • , Wei Zhu
    •  & Yusuf A Hannun

  • Article
    | Open Access

    Hypoxia inducible factor (HIF)-2α transcription factor is mutated in polycythemia and various neuroendocrine tumors. Here the authors present the crystal structure of a HIF-2α peptide bound to the pVHL-elongin B-elongin C (VBC) heterotrimeric complex and propose a classification scheme for HIF-2α mutations that helps to predict disease phenotype outcome.

    • Daniel Tarade
    • , Claire M. Robinson
    •  & Michael Ohh

  • Article
    | Open Access

    Aberrant glycosylation patterns on cancer cells promote several pro-tumorigenic functions, including enhancing tumor cell proliferation. Here the authors provide data that show melanoma cells downregulate GCNT2 with consequent loss of I-branched glycans; this leads to the formation of extended i-linear glycans and enhances melanoma growth via increases, in part, by IGF-1- and extracellular matrix-induced signaling.

    • Jenna Geddes Sweeney
    • , Jennifer Liang
    •  & Charles J. Dimitroff

  • Article
    | Open Access

    Pineoblastoma is a highly aggressive and rare childhood brain cancer, and the genetic drivers of sporadic pineoblastoma are unknown. Here, the authors genomically interrogated pediatric and adult pineoblastomas and found novel variants including recurrent homozygous deletions of DROSHA.

    • Matija Snuderl
    • , Kasthuri Kannan
    •  & Matthias A. Karajannis

  • Article
    | Open Access

    Chemotherapy agents are prone to producing severe side-effects, and their sequestration prior to their entering of the circulatory system is thus highly desirable. Here, the authors functionalize iron oxide nanoparticles with genomic DNA and achieve sequestration of doxorubicin, cisplatin, and epirubicin from biological solutions.

    • Carl M. Blumenfeld
    • , Michael D. Schulz
    •  & Robert H. Grubbs

  • Article
    | Open Access

    Tumours produce soluble factors that contribute to the expansion of Gr-1+CD11b+ immature myeloid cells with TGFβ dependent immune suppressive function. Here, the authors show miR-130a and miR-145 target TβRII and reprogram these cells by altering the cytokine microenvironment, improving anti-tumour immunity and inhibiting metastasis in preclinical mouse models.

    • Hiroki Ishii
    • , Suman K. Vodnala
    •  & Li Yang

  • Article
    | Open Access

    Signet-ring cell carcinoma (SRCC) is a unique type of gastric cancer with no prognostic features. Here, the authors report a CLDN18-ARHGAP26/6 gene fusion in patients with a high signet-ring cell content, poor survival outcomes, and who experience no benefit from platinum/fluoropyrimidines-based chemotherapy.

    • Yang Shu
    • , Weihan Zhang
    •  & Jiankun Hu

  • Article
    | Open Access

    Activation of an immune response is critical for the efficacy of cancer therapies. Here, the authors show that combination of ROCK inhibitor with chemotherapeutics that induce immunogenic cell death of cancer cells leads to increased dendritic cells’ maturation and synergistic CD8+ cytotoxic T cell priming and infiltration into the tumours, leading to suppressed tumour growth and improved overall survival in syngeneic and genetically engineered tumour models.

    • Gi-Hoon Nam
    • , Eun Jung Lee
    •  & In-San Kim

  • Article
    | Open Access

    Lung squamous carcinomas (LUSC) are poorly molecularly characterized, but sub-populations show promising response to immune checkpoint inhibitors. Here, the authors identify a subset of LUSC characterized by infiltration of inflammatory monocytes, where metastasis is linked to Factor XIIIA promoting fibrin cross-linking.

    • Alessandro Porrello
    • , Patrick L. Leslie
    •  & Chad V. Pecot

  • Article
    | Open Access

    In leukemia, diverse fusion proteins involving the MLL gene can drive oncogenic activity. Here, the authors describe a dependency of MLL-leukemia cells on the methyltransferase SETD2 to maintain genomic integrity during leukemia initiation and maintenance.

    • Anna Skucha
    • , Jessica Ebner
    •  & Florian Grebien

  • Article
    | Open Access

    Hypermutated tumors respond more favorably to checkpoint inhibitor-based immune therapy. Here, the authors describe a new hypermutated phenotype due to germline mutations and subsequent somatic loss of heterozygosity of MBD4, and a dramatic response to the PD-1 inhibitor pembrolizumab in a patient with a MBD4-inactivated hypermutated uveal melanoma.

    • Manuel Rodrigues
    • , Lenha Mobuchon
    •  & Marc-Henri Stern

  • Article
    | Open Access

    The mechanisms of PARP inhibitor (PARPi) resistance are poorly understood. Here the authors employ a CRISPR mutagenesis approach to identify PARP1 mutants causing PARPi resistance and find that PARP1 mutations are tolerated in BRCA1 mutated cells, suggesting alternative resistance mechanisms.

    • Stephen J. Pettitt
    • , Dragomir B. Krastev
    •  & Christopher J. Lord

  • Article
    | Open Access

    A central question in cancer research is how specific driver mutations are acquired and maintained during cancer development. Here Temko et al. use public sequencing data to infer the effect of mutation and selection on a set of driver mutations and suggest that selection frequently dominates.

    • Daniel Temko
    • , Ian P. M. Tomlinson
    •  & Trevor A. Graham

  • Article
    | Open Access

    The oligometastasis hypothesis suggests certain metastases are limited in extent and curable with focal therapies. Here they identify three integrated molecular subtypes of colorectal cancer liver metastasis, which complement clinical risk stratification to distinguish the subset of oligometastatic patients.

    • Sean P. Pitroda
    • , Nikolai N. Khodarev
    •  & Ralph R. Weichselbaum

  • Article
    | Open Access

    Genomic aberrations contribute to the development of cancer; however, their interdependence remains poorly understood. Here the authors analyze liver cancer samples to find correlation between epigenetic features and genetic aberrations including somatic substitutions, mutation signatures, and HBV integration sites.

    • Natsuko Hama
    • , Yasushi Totoki
    •  & Tatsuhiro Shibata

  • Article
    | Open Access

    Most breast cancer patients are estrogen receptor positive and thus benefit from treatments that inhibit estrogen production; however, one third of tamoxifen-treated patients develops resistance and relapse. Here the authors show that tamoxifen resistant cells are resistant to chemotherapy because of BARD1 and BRCA1 upregulation.

    • Yinghua Zhu
    • , Yujie Liu
    •  & Qiang Liu

  • Article
    | Open Access

    The vascular structure of tumors impacts diagnosis, prognosis and drug response; however, imaging methods to analyse this important feature have been hindered by spatial resolution limitations. Here the authors present a tool called motion model ultrasound localization microscopy to morphologically and functionally characterize fine vascular networks in tumors at super-resolution.

    • Tatjana Opacic
    • , Stefanie Dencks
    •  & Fabian Kiessling

  • Article
    | Open Access

    Inhibitors of mutant isocitrate dehydrogenase 1 (IDH1) entered recently clinical trials for treatment of gliomas. Here, the authors apply a MRS imaging method for 2HG detection and assessement of the pharmacodynamic effects of the mutant IDH1 inhibitor (IDH305) in 8 mutant IDH1 glioma patients.

    • Ovidiu C. Andronesi
    • , Isabel C. Arrillaga-Romany
    •  & Tracy T. Batchelor

  • Article
    | Open Access

    Histone chaperone ASF1A is often dysregulated in cancers, however the regulation of its abundance is unclear. Here, the authors show that USP52 promotes ASF1A stability through deubiquitination while impairment of this stability reduces breast tumorigenesis and confers sensitivity to DNA damage.

    • Shangda Yang
    • , Ling Liu
    •  & Lei Shi

  • Article
    | Open Access

    Resistance to chemotherapy is a serious issue that can be influenced by RNA epigenetics and chromatin structure. Here, the authors show in leukaemia cells that RNA 5-methylcytosine (RNA:m5C) and RNA:m5C methyltransferases (RCMTs) mediate chromatin structures that can modulate 5-Azacitidine response and resistance.

    • Jason X. Cheng
    • , Li Chen
    •  & James W. Vardiman

  • Article
    | Open Access

    Understanding of molecular events in cancer requires proteome-level characterisation. Here, proteome profiling of patient samples representing primary and progressed prostate cancer enables the authors to identify pathway alterations that are not reflected at the genomic and transcriptomic levels.

    • Leena Latonen
    • , Ebrahim Afyounian
    •  & Tapio Visakorpi

  • Article
    | Open Access

    Triple negative breast cancers harbor multiple copy number aberrations driving gene expression changes thought to underpin their malignant phenotypes. Here the authors integrate these features, finding and functionally validating 37 gene addictions among which they identify the mechanism of addiction to KIFC1, a potential selective drug target.

    • Nirmesh Patel
    • , Daniel Weekes
    •  & Andrew N. J. Tutt

  • Article
    | Open Access

    Eya proteins are characterised by phosphatase activity associated with both the evolutionary conserved region and the less conserved N-terminal domain (NTD). Here the authors show that NTD mediates the interaction with PP2A and regulates c-Myc phosphorylation and stability, potentially switching PP2A from a tumour suppressor to an oncogene.

    • Lingdi Zhang
    • , Hengbo Zhou
    •  & Heide L Ford

  • Article
    | Open Access

    A critical determinant of tumor eradication by adoptive immunotherapy is the tumor associated antigen recognized by cytotoxic T lymphocytes. Here the authors generate ex vivo autologous cytotoxic T lymphocytes by exposure to antigens induced by DNA demethylation and report the results of a phase 1 trial of 25 patients with recurrent glioblastoma multiforme with tumor regression in three patients.

    • Alexei F. Kirkin
    • , Karine N. Dzhandzhugazyan
    •  & Walter Fischer

  • Article
    | Open Access

    Circulating tumor DNA (ctDNA) may provide a prediction of treatment response, but could be impacted by tumor heterogeneity. Here, the authors investigate ctDNA in CDK4/6 inhibitor treatment in advanced breast cancer, finding ctDNA levels predict progression-free survival and anticipate clonal selection.

    • Ben O’Leary
    • , Sarah Hrebien
    •  & Nicholas C. Turner

  • Article
    | Open Access

    Hepatocellular-cholangiocarcinoma (H-ChC) is a rare subtype of liver cancer with features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Here, the authors utilize whole exome sequencing to highlight the monoclonal origin and stemness of H-ChC, as well as substantial intratumoral heterogeneity.

    • Anqiang Wang
    • , Liangcai Wu
    •  & Haitao Zhao

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