News & Comment

  • Research Highlight |

    In a study published in Nature, Perez-Ruiz et al. report that prophylactic tumour necrosis factor (TNF) blockade reduces gastrointestinal immune-related adverse events in mice treated with dual immune-checkpoint inhibition, providing a clear preclinical rationale for the clinical investigation of such strategies.

    • Conor A. Bradley
  • Research Highlight |

    Esposito et al. describe a mechanism for the simultaneous induction of mesenchymal-to-epithelial transition and stem cell traits in disseminating breast cancer cells in the bone, and provide therapeutic opportunities to prevent initiation of bone metastasis.

    • Ulrike Harjes
  • Research Highlight |

    Benbenishty et al. find that prophylactic administration of CpG-C, a Toll-like receptor 9 agonist, significantly reduces the development of brain metastasis in preclinical mouse models via the activation of microglial cells that kill and phagocytose the tumour cells.

    • Maria Giuseppina Baratta
  • Research Highlight |

    Three studies have delved into the molecular mechanisms behind the metabolic reprogramming of tumour-associated macrophages, which have consequences for tumour progression and therapeutic response and resistance.

    • Anna Dart
  • Research Highlight |

    Four papers report that cancer cells with microsatellite instability, which arises owing to defects in DNA mismatch repair, are selectively vulnerable to knockout of WRN, a RecQ family DNA helicase that could potentially be targeted with small molecules.

    • Sarah Seton-Rogers
  • Research Highlight |

    In a study published in Nature Medicine, Malehmir et al. have identified how platelet recruitment contributes to the development of nonalcoholic steatohepatitis and hepatocellular carcinoma in response to high-fat diets in mice.

    • Ulrike Harjes
  • Research Highlight |

    Omomyc, a MYC dominant-negative gene product that is used to inhibit MYC for research purposes, can penetrate cancer cells in vitro and in vivo, bringing it closer to evaluation in the clinic.

    • M. Teresa Villanueva
  • Research Highlight |

    In a study published in Nature Biotechnology, Aalipour et al. have engineered macrophages to create biocompatible diagnostic sensors that can detect tumours as small as 25–50 mm3 in mice, even with co-occurring inflammation.

    • Anna Dart
  • Research Highlight |

    Parada and colleagues have identified a novel small-molecule inhibitor of oxidative phosphorylation, which exerts cancer-cell-specific toxicity and inhibits glioblastoma growth in mouse models.

    • Sarah Crunkhorn
  • Research Highlight |

    Two studies show that in the presence of KRAS pathway inhibition, KRAS-mutant pancreatic ductal adenocarcinomas become dependent on autophagy for survival. Removing this protective mechanism through combining MEK or ERK inhibitors with inhibitors of autophagy is likely to be therapeutically beneficial.

    • Sarah Seton-Rogers
  • Research Highlight |

    Failure of anticancer immune responses is often due to T cell dysfunction, but the molecular mechanisms underlying this are incompletely understood. Two papers in Nature now identify NR4A transcription factors as key drivers of T cell dysfunction.

    • Alexandra Flemming
  • Research Highlight |

    Hu et al. demonstrate that in pancreatic cells, genomic instability and mutations in KRAS, which drive carcinogenesis, can be promoted by high glucose-induced deregulation of deoxyribonucleotide synthesis.

    • Ulrike Harjes
  • Research Highlight |

    In a study published in Nature, Obradović et al. have identified that breast cancer progression in mice is associated with increased levels of stress hormones resulting in activation of the glucocorticoid receptor at secondary sites, enhanced colonization and decreased survival.

    • Anna Dart
  • Research Highlight |

    Elia et al. show that breast cancer cells in the lung metastatic niche are dependent on pyruvate uptake to promote extracellular matrix remodelling and metastatic growth, which can be targeted therapeutically.

    • Ulrike Harjes
  • Research Highlight |

    Singhal et al. characterized tumour-infiltrating monocyte and macrophage lineage cells in patients with early stage lung cancer and found that, contrary to data in mouse models, the function of these cells might not be primarily immunosuppressive.

    • Maria Giuseppina Baratta
  • Research Highlight |

    Miller, Sen et al. show that exhausted T cells in tumours contain distinct subpopulations, one of which is long-lived and persistent and, in response to immune checkpoint blockade, can give rise to short-lived cytotoxic T cells that exert tumour control.

    • Ulrike Harjes
  • Comment |

    In an effort to prevent bullying and harassment in the research sector, funding bodies have introduced policies to promote a positive research culture. Here, Sue Russell and Iain Foulkes comment on what this means for researchers.

    • Sue Russell
    •  & Iain Foulkes
  • Research Highlight |

    In a study published in Nature, Messal, Alt et al. report the use of a new imaging technique that has shed light on the morphology of developing tumours within pancreatic ducts.

    • Sarah Seton-Rogers
  • Research Highlight |

    Lee et al. show that in a mouse model of melanoma, tumour cells that spread to the draining lymph node adapt to the fatty acid-rich environment in the lymph node by activation of YAP signalling and fatty acid oxidation.

    • Ulrike Harjes
  • Research Highlight |

    Two independent studies have advanced our understanding of local microbiota immunomodulation and provided insight into how potential manipulation of microbial composition could transform treatment strategies for patients with cancer.

    • Anna Dart
  • Editorial |

    How does a Nature Reviews Cancer Review or Perspectives article move from an idea to a published article? Here, in the spirit of transparency, we provide some insights into this process.

  • Research Highlight |

    A new study has shown that endovascular progenitor cells, which are precursors of the endothelial cells that make up tumour blood vessels, are inhibited by conditional ablation of Notch signalling, leading to inhibition of melanoma metastasis in mice.

    • Jordan Hindson
  • Research Highlight |

    Ruscetti, Leibold, Bott et al. show that the growth of Kras-mutant lung tumours is sensitive to combined blockade of KRAS effectors. This was dependent on induction of the senescence-activated phenotype in cancer cells, followed by natural killer cell-mediated cell clearance.

    • Ulrike Harjes
  • Research Highlight |

    Two phase I studies, recently published in Nature, show that the administration of personalized vaccines to newly diagnosed patients with glioblastoma generates tumour-reactive T cells that infiltrate glioblastomas, turning them into ‘hot’ tumours potentially susceptible to further immunotherapy approaches.

    • Maria Giuseppina Baratta
  • Research Highlight |

    Two studies show that cancer cells contain sufficient quantities of immunostimulatory nucleic acids to trigger interferon signalling, increase antitumour immunity and overcome resistance to checkpoint blockade. Loss of the RNA-editing enzyme ADAR1 enables tumour cells to sense these innate ligands.

    • M. Teresa Villanueva
  • Research Highlight |

    Gkountela et al. have identified that circulating tumour cell (CTC) clusters from patients and mouse models with breast cancer have a distinct DNA methylation profile from that of single CTCs, which together with the phenotypic difference represent a targetable therapeutic vulnerability of metastasis.

    • Anna Dart
  • Research Highlight |

    Keklikoglou et al. show that, in mouse models of chemoresistant breast cancer, paclitaxel and doxorubicin trigger the production of tumour-derived extracellular vesicles with pro-metastatic properties that are dependent on annexin A6.

    • Katharine H. Wrighton
  • Comment |

    Cancer brings an increasing health and economic burden worldwide, and the greatest impact is had on the most vulnerable populations. In this Comment, Christopher Wild discusses the need for investment to ensure long-term cancer prevention strategies.

    • Christopher P. Wild
  • Research Highlight |

    Neal et al. have successfully established patient-derived organoids of tumour epithelia retaining native immune cells, thereby recapitulating tumour microenvironment diversity and enabling immuno-oncology studies.

    • Anna Dart
  • Research Highlight |

    Two studies suggest that caution is warranted in attempts to inhibit the histone methyltransferase G9a for cancer therapy, as its loss can promote tumour development and evolution.

    • Sarah Seton-Rogers
  • Research Highlight |

    Laumont, Vincent et al. have developed a proteogenomic strategy for high-throughput mass spectrometry-based discovery of aberrantly expressed tumour-specific antigens from non-coding sequences as well as mutated tumour-specific antigens encoded by all genomic regions, thereby expanding the number of targetable antigens that can be used for cancer vaccine development.

    • Anna Dart
  • Research Highlight |

    Poillet-Perez et al. show that autophagy in non-tumour tissues in tumour-bearing mice inhibits release of the arginine-degrading enzyme arginase 1 (ARG1) from the liver into circulation, thereby maintaining the levels of arginine in the circulation and contributing to tumour growth.

    • Ulrike Harjes
  • Research Highlight |

    Lim et al. show that there is an association between germline genetic variants and the immune features of a tumour, and that genetic background might affect responses to immunotherapy.

    • Maria Giuseppina Baratta
  • Research Highlight |

    Two studies published in Cell have characterized the inhibitory immune receptor NKG2A expressed on cytotoxic lymphocytes, such as natural killer cells and CD8+ T cells, as a novel checkpoint for cancer immunotherapy.

    • Anna Dart
  • Research Highlight |

    New findings published in Nature Medicine highlight a role for the anti-CTLA4 antibody ipilimumab when combined with radiotherapy in treating metastatic NSCLC.

    • Jordan Hindson
  • Editorial |

    Cancer research and Nature Reviews Cancer have both experienced many highs and lows in 2018, and we look forward to what 2019 has in store.

  • Research Highlight |

    Assi et al. have generated multi-omics data on leukaemic blasts from acute myeloid leukaemia (AML) patients with defined genetic alterations. These data provide a comprehensive overview of the specific transcriptional and signalling networks in certain AML subtypes.

    • Katharine H. Wrighton
  • Research Highlight |

    Lane et al. have shown that interferon-γ (IFNγ)-mediated activation of the lymphatic vasculature, as a non-haematopoietic component of the tumour stroma, serves to limit local CD8+ T cell accumulation in melanoma in mice as a mechanism of immune suppression.

    • Anna Dart
  • Research Highlight |

    Wang et al. demonstrate that increased flux of calcium derived from osteogenic cells into cancer cells promotes early-stage bone colonization. Calcium signalling in cancer cells can be targeted by arsenic trioxide, thereby reducing bone metastasis progression.

    • Ulrike Harjes
  • Research Highlight |

    A study in Science reports the genome-wide chromatin accessibility profiles across 23 cancer types from The Cancer Genome Atlas and notably increases the number of known gene regulatory elements.

    • Michelle Trenkmann
  • Research Highlight |

    Song et al. show that in patients with ovarian cancer, intratumoural T cells and ascites-resident T cells experience endoplasmic reticulum stress triggered by activation of IRE1α–XBP1 signalling, leading to reduced antitumour activity.

    • Ulrike Harjes
  • Research Highlight |

    Xie et al. have shown that a recently reported DNA modification in mammals, repressive N6-methyladenine, is enriched in human glioblastoma and targeting this modification can reduce cancer cell growth by restricting chromatin accessibility at oncogenic loci.

    • Anna Dart
  • Research Highlight |

    Grohmann, Wiede et al. report that obesity-associated nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) can be driven by independent pathways. In particular, HCC can be driven by STAT3 signalling, independently from STAT1-driven NASH.

    • Ulrike Harjes
  • Research Highlight |

    Martincorena, Fowler et al. have characterized the mutational landscape of normal oesophageal tissue during ageing, which has provided important insights into early cancer development.

    • Anna Dart
  • Research Highlight |

    Two studies from Ashani Weeraratna’s group have examined how changes in the skin microenvironment associated with ageing promote melanoma metastasis and modify immune infiltration.

    • Sarah Seton-Rogers
  • Research Highlight |

    Ye et al. show that leukaemia cells induce insulin resistance in the host to limit glucose consumption by healthy tissues, thereby augmenting the amount of available glucose for cancer growth.

    • Maria Giuseppina Baratta
  • Research Highlight |

    Transcription elongation supported by the super elongation complex, and histone H3 lysine 9 methylation and gene repression by G9a mediate the oncogenic function of MYC.

    • Eytan Zlotorynski
  • Research Highlight |

    Albrengues et al. have characterized a mechanism by which sustained lung inflammation can cause a switch from cancer dormancy to metastasis through the induction of neutrophil extracellular traps.

    • Anna Dart