Browse Articles

  • Perspective |

    This Opinion article provides an overview of the mechanisms that regulate sensitivity to ferroptosis in cancer cells and how the modulation of metabolic pathways controlling ferroptosis might reshape the tumour niche, leading to an immunosuppressive microenvironment that promotes tumour progression.

    • José Pedro Friedmann Angeli
    • , Dmitri V. Krysko
    •  & Marcus Conrad
  • Review Article |

    Tertiary lymphoid structures (TLSs) form outside of lymphoid tissues at sites of chronic inflammation, including tumours. This Review describes the evidence demonstrating that TLSs are critical for generating antitumour immune responses and are associated with better prognosis in certain cancer types. It also presents potential strategies aimed at inducing TLS neogenesis to improve clinical responses in poorly immunogenic cancers.

    • Catherine Sautès-Fridman
    • , Florent Petitprez
    • , Julien Calderaro
    •  & Wolf Herman Fridman
  • Perspective |

    For any given cancer type, there are patients who have exceptionally favourable or atypically poor responses to treatment and overall survival. This Opinion article outlines approaches to identify and study these patients at the extremes of the spectrum with a view to gain insights that will be applicable to the wider patient population.

    • Flurina A. M. Saner
    • , Alan Herschtal
    • , Brad H. Nelson
    • , Anna deFazio
    • , Ellen L. Goode
    • , Susan J. Ramus
    • , Ahwan Pandey
    • , Jessica A. Beach
    • , Sian Fereday
    • , Andrew Berchuck
    • , Stephanie Lheureux
    • , Celeste Leigh Pearce
    • , Paul D. Pharoah
    • , Malcolm C. Pike
    • , Dale W. Garsed
    •  & David D. L. Bowtell
  • 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
  • Review Article |

    Alterations of the cyclin-dependent kinase (CDK)–RB–E2F axis occur in virtually all cancers and result in heightened oncogenic E2F activity and uncontrolled proliferation. This Review discusses the activities of E2F proteins in cancer and therapeutic strategies to target this oncogenic pathway.

    • Lindsey N. Kent
    •  & Gustavo Leone
  • 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
  • Perspective |

    The implementation of screening tests for certain cancers has led to the phenomenon of overdiagnosis, whereby a cancer is diagnosed that would otherwise not go on to cause symptoms or death. This Opinion article discusses the effects of overdiagnosis and emerging strategies to reduce overdiagnosis of indolent cancers through an understanding of tumour biology and the tumour microenvironment.

    • Sudhir Srivastava
    • , Eugene J. Koay
    • , Alexander D. Borowsky
    • , Angelo M. De Marzo
    • , Sharmistha Ghosh
    • , Paul D. Wagner
    •  & Barnett S. Kramer
  • Perspective |

    This Opinion discusses three different mechanisms by which high-dose vitamin C can be selectively toxic to cancer cells. These findings from preclinical studies will be beneficial for the design of clinical trials testing high-dose vitamin C as an anticancer therapy.

    • Bryan Ngo
    • , Justin M. Van Riper
    • , Lewis C. Cantley
    •  & Jihye Yun
  • 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
  • Review Article |

    Recurrent oncogenic chromosomal rearrangements frequently involve genes required for chromatin regulation and transcriptional control. This Review discusses mechanistic insights into the chromatin-based functions of many of these oncogenic fusion proteins that are guiding the design of new therapeutic approaches.

    • Gerard L. Brien
    • , Kimberly Stegmaier
    •  & Scott A. Armstrong
  • 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
  • Perspective |

    This Opinion, written by many leading experts in small cell lung cancer (SCLC) research, proposes a new model of SCLC subtypes defined by differential expression of four key transcription regulators. Such classification should help to focus and accelerate therapeutic research.

    • Charles M. Rudin
    • , John T. Poirier
    • , Lauren Averett Byers
    • , Caroline Dive
    • , Afshin Dowlati
    • , Julie George
    • , John V. Heymach
    • , Jane E. Johnson
    • , Jonathan M. Lehman
    • , David MacPherson
    • , Pierre P. Massion
    • , John D. Minna
    • , Trudy G. Oliver
    • , Vito Quaranta
    • , Julien Sage
    • , Roman K. Thomas
    • , Christopher R. Vakoc
    •  & Adi F. Gazdar
  • 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
  • Perspective |

    The existence of extrachromosomal DNA (ecDNA) in cancer was first described decades ago, but recent reports of oncogene amplification on ecDNA have reinvigorated interest in this field. This Perspectives article discusses the potential implications of oncogene amplification on ecDNA in cancer.

    • Roel G. W. Verhaak
    • , Vineet Bafna
    •  & Paul S. Mischel
  • Review Article |

    In addition to cancer cell-intrinsic effects, tumour growth can be regulated by cellular and molecular cues from the local tissue environment. This Review discusses how differences in cellular components and composition between tissue sites may influence the antitumour immune response, with potential implications for the design of therapeutic strategies.

    • Hélène Salmon
    • , Romain Remark
    • , Sacha Gnjatic
    •  & Miriam Merad
  • 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
  • Review Article |

    Inflammasome signalling in myeloid cells protects against microbial infections. Aberrant inflammasome signalling promotes chronic inflammation, which contributes to tumorigenesis. This Review presents an overview of the diverging roles of inflammasomes in cancer and discusses its targeting potential in anticancer therapy.

    • Rajendra Karki
    •  & Thirumala-Devi Kanneganti
  • Progress |

    In this Progress article, Wu, Jusiak and Lu discuss how synthetic biology-based design principles can be applied to living cells to overcome key challenges in current cancer therapy and generate more robust, specific and effective gene circuit therapies.

    • Ming-Ru Wu
    • , Barbara Jusiak
    •  & Timothy K. Lu
  • 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
  • Review Article |

    This Review discusses recent work demonstrating that immune checkpoint inhibitor efficacy is affected by a combination of factors involving tumour genomics, host germline genetics, programmed cell death 1 ligand 1 (PDL1) levels and other features of the tumour microenvironment, as well as the gut microbiome.

    • Jonathan J. Havel
    • , Diego Chowell
    •  & Timothy A. Chan
  • 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
  • Review Article |

    In this Review, Jones et al. present the evidence that epigenetic therapies can induce the expression of endogenous retroviruses and cancer–testis antigens normally silenced by DNA methylation in most somatic cells. As a consequence, a state of viral mimicry is evoked in cancer cells, leading to an innate immune response. Understanding this process has implications for combination therapy with epigenetic drugs and immunotherapies to improve clinical outcomes for patients with cancer.

    • Peter A. Jones
    • , Hitoshi Ohtani
    • , Ankur Chakravarthy
    •  & Daniel D. De Carvalho
  • 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
  • Review Article |

    This Review discusses how increased catabolism of the amino acids tryptophan and arginine driven by inflammatory processes in the tumour microenvironment contributes to tumorigenesis, suppression of antitumour immunity and potentially neurological comorbidities associated with cancer.

    • Henrique Lemos
    • , Lei Huang
    • , George C. Prendergast
    •  & Andrew L. Mellor
  • 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
  • Review Article |

    This Review discusses mechanisms for the increased cancer risk in patients with rare ribosomopathies. As such, defects in ribosome biogenesis that occur in ribosomopathies can mediate carcinogenesis, and mutations in ribosome biogenesis genes have been reported to drive sporadic cancers.

    • Anna Aspesi
    •  & Steven R. Ellis