Latest Reviews

  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Review Article |

    In vitro cancer models often fail to faithfully recapitulate the local tissue and organ microenvironment. Organs-on-chips can overcome this limitation and better mimic in vivo cancer phenotypes. This Review outlines the advances that have been made with this technology and explains the challenges that must be overcome to see its implementation into drug development pipelines and clinical cancer care.

    • Alexandra Sontheimer-Phelps
    • , Bryan A. Hassell
    •  & Donald E. Ingber
  • Perspective |

    Genomic instability in cancer models presents a major challenge in the design and reproducibility of research and its clinical translation. This Opinion article discusses the causes and consequences of intra-tumour genomic heterogeneity and instability in commonly used models and implications thereof.

    • Uri Ben-David
    • , Rameen Beroukhim
    •  & Todd R. Golub
  • Review Article |

    This Review discusses how excessive signal transducer and activator of transcription 3 (STAT3) activation within cancer cells and cells of the tumour microenvironment can be viewed as a neoplastic mimic of an inflammation-driven repair response that promotes tumour progression.

    • Jennifer Huynh
    • , Ashwini Chand
    • , Daniel Gough
    •  & Matthias Ernst
  • Review Article |

    This Review discusses causal germline variants in prostate cancer identified through genome-wide association studies (GWAS) and post-GWAS analyses. The latter are vital to identify causal variants and molecular mechanisms by which these variants promote prostate tumorigenesis, with potential clinical applications.

    • Samaneh Farashi
    • , Thomas Kryza
    • , Judith Clements
    •  & Jyotsna Batra
  • Review Article |

    In this Review, Altorki et al. discuss how the tumour-reprogrammed lung microenvironment can contribute to primary lung tumour progression as well as lung metastasis from extrapulmonary neoplasms by promoting inflammation, angiogenesis, immune modulation and therapeutic responses.

    • Nasser K. Altorki
    • , Geoffrey J. Markowitz
    • , Dingcheng Gao
    • , Jeffrey L. Port
    • , Ashish Saxena
    • , Brendon Stiles
    • , Timothy McGraw
    •  & Vivek Mittal
  • Review Article |

    This Review discusses the evidence that whole-genome duplication as a consequence of cytokinesis failure can contribute to tumorigenesis.

    • Susanne M. A. Lens
    •  & René H. Medema
  • Perspective |

    This Opinion argues that understanding the interactions between cells that occur in tumours requires concepts from evolutionary game theory. Game theory can provide insights into the stability of cooperation among cells in a tumour and how this might be used therapeutically.

    • Marco Archetti
    •  & Kenneth J. Pienta
  • Review Article |

    This Review discusses the interdependencies of mTOR signalling and metabolism pathways in cancer and how metabolic reprogramming in response to changes in mTOR signalling and vice versa can sustain tumorigenicity. The authors highlight therapeutic opportunities when targeting metabolism and mTOR.

    • Dirk Mossmann
    • , Sujin Park
    •  & Michael N. Hall
  • Perspective |

    This Opinion describes cell-in-cell processes in cancer, providing insight into their functional purpose in tumour tissue. Entosis is a unique process in which cancer cells are actively invaded by other cells, conferring them a competitive advantage that may drive cancer evolution.

    • Stefano Fais
    •  & Michael Overholtzer
  • Perspective |

    In this Opinion, Li et al. put forward the idea that there is a narrow window or ‘sweet spot’ in which oncogenic RAS signalling can promote tumour initiation in normal cells and present the evidence that RAS mutation patterns are the product of selection for optimal RAS mutations to achieve the ideal level of signalling.

    • Siqi Li
    • , Allan Balmain
    •  & Christopher M. Counter
  • Review Article |

    Therapy with live tumour-targeting bacteria represents a unique opportunity to address the limitations associated with molecularly targeted therapies and immunotherapies. In this Review, Zhou et al. discuss the benefits and challenges of this approach and outline advances in the engineering of bacteria, which have the potential to improve safety and efficacy.

    • Shibin Zhou
    • , Claudia Gravekamp
    • , David Bermudes
    •  & Ke Liu
  • Perspective |

    This Opinion discusses the potential of fasting and fasting-mimicking diets to help overcome toxicities induced by anticancer therapy. The differential response of normal and cancer cells undergoing starvation is argued to make normal cells less sensitive to therapy-induced toxicity, while cancer cells become more sensitive to therapy-induced cell death.

    • Alessio Nencioni
    • , Irene Caffa
    • , Salvatore Cortellino
    •  & Valter D. Longo
  • Review Article |

    This Review discusses the 2018 Catalogue of Somatic Mutations in Cancer (COSMIC) Cancer Gene Census (CGC), an expert-curated description of human cancer genes, which has recently been expanded to include functional descriptions of how each gene contributes to cancer.

    • Zbyslaw Sondka
    • , Sally Bamford
    • , Charlotte G. Cole
    • , Sari A. Ward
    • , Ian Dunham
    •  & Simon A. Forbes
  • Review Article |

    This Review discusses how cells with stem cell characteristics often serve as the tumour cell of origin, as they are preferentially primed for transformation. Furthermore, the activation of stem cell programmes can be crucial for promoting cancer progression and therapy resistance.

    • Nikki K. Lytle
    • , Alison G. Barber
    •  & Tannishtha Reya
  • Review Article |

    This Review discusses the reprogramming of the urea cycle, the main metabolic liver pathway for nitrogen disposal, in cancer cells. The authors provide insight into the metabolic advantages and therapeutic opportunities stemming from urea cycle enzyme perturbations in cancer.

    • Rom Keshet
    • , Peter Szlosarek
    • , Arkaitz Carracedo
    •  & Ayelet Erez
  • Review Article |

    Cancer is ubiquitous in wildlife and is an increasing concern for endangered species. This Review discusses the impact of cancer on animal species and highlights how studying these effects could reveal shared mechanisms of cancer predisposition between animals and humans.

    • Patricia A. Pesavento
    • , Dalen Agnew
    • , Michael K. Keel
    •  & Kevin D. Woolard
  • Review Article |

    This Review discusses nutrient scavenging, a process by which cancer cells use macromolecules from their environment to fuel cell metabolism and growth even when nutrients are limiting.

    • Brendan T. Finicle
    • , Vaishali Jayashankar
    •  & Aimee L. Edinger
  • Review Article |

    In this Review, Di Virgilio et al. describe how extracellular ATP and P2 purinergic signalling can shape the tumour microenvironment to both promote and restrain tumour progression and outline the opportunities to harness nucleotide receptor signalling as an anticancer strategy.

    • Francesco Di Virgilio
    • , Alba Clara Sarti
    • , Simonetta Falzoni
    • , Elena De Marchi
    •  & Elena Adinolfi
  • Review Article |

    In this Review, Hamidi and Ivaska discuss the contribution of integrins to the different steps of cancer progression, highlighting some of the recently identified unconventional roles of integrins and novel opportunities to target integrin signalling.

    • Hellyeh Hamidi
    •  & Johanna Ivaska
  • Perspective |

    This Opinion provides insight into the potential of targeting the replication stress response in cancer and discusses the strategy of inhibiting ataxia telangiectasia and Rad3-related protein (ATR) and the need for reliable biomarkers to enable patient stratification.

    • Emilio Lecona
    •  & Oscar Fernandez-Capetillo
  • Perspective |

    This Opinion proposes that temporal variations in intratumoural blood flow are the result of eco-evolutionary dynamics. It describes adaptive strategies to stochastically varying environments that may strongly affect observed cancer phenotypes and clinical outcomes including formation of metastases and response to treatment.

    • Robert J. Gillies
    • , Joel S. Brown
    • , Alexander R. A. Anderson
    •  & Robert A. Gatenby
  • Review Article |

    This Review discusses the origins of squamous cell carcinoma (SCC), with a focus on skin, lung, oesophageal and head and neck cancer, and describes how oncogenic mutations and the cell of origin cooperate in determining the rise of SCC.

    • Adriana Sánchez-Danés
    •  & Cédric Blanpain
  • Perspective |

    This Opinion discusses the role of the primary cilium as a platform for pathways implicated in cancer and how changes in the ciliation of cells in the tumour microenvironment can affect cancer progression.

    • Hanqing Liu
    • , Anna A. Kiseleva
    •  & Erica A. Golemis
  • Perspective |

    In this Opinion, Joshi et al. argue that in cancer cells, a state of chaperome hyperconnectivity is obtained by increasing the interaction strength among chaperome machinery members. These chaperome scaffolding platforms act to increase the functional diversity of oncogenic processes and have implications for the development of chaperome inhibitors.

    • Suhasini Joshi
    • , Tai Wang
    • , Thaís L. S. Araujo
    • , Sahil Sharma
    • , Jeffrey L. Brodsky
    •  & Gabriela Chiosis
  • Review Article |

    In this Review, Greaves describes the evidence supporting the model that infections early in life reduce the risk of childhood common B cell precursor acute lymphoblastic leukaemia (BCP-ALL) development. Given this evidence, paediatric BCP-ALL may be a preventable cancer.

    • Mel Greaves
  • Perspective |

    In this Opinion article, Hosny et al. discuss the application of artificial intelligence to image-based tasks in the field of radiology and consider the advantages and challenges of its clinical implementation.

    • Ahmed Hosny
    • , Chintan Parmar
    • , John Quackenbush
    • , Lawrence H. Schwartz
    •  & Hugo J. W. L. Aerts