Review Articles

  • Review Article |

    This Review outlines the ways in which leukaemic stem cells (LSCs) take advantage of normal haematopoietic stem cell properties to promote survival and expansion in myeloid leukaemogenesis. Opportunities for treatment of this disease by targeting LSC-specific mechanisms are also discussed.

    • Masayuki Yamashita
    • , Paul V. Dellorusso
    • , Oakley C. Olson
    •  & Emmanuelle Passegué
  • Review Article |

    This Review discusses oncoproteins known to cause both cancer and congenital disorders, and the biology of oncoproteins in both transformed and untransformed tissues, exploring the fundamentals of genetics, signalling and the pathogenesis that underlie oncoprotein duality.

    • Pau Castel
    • , Katherine A. Rauen
    •  & Frank McCormick
  • Review Article |

    After synthesis, all RNA molecules are subject to covalent modifications. This Review presents the evidence that RNA modification pathways are misregulated in cancer and suggests that they may be ideal targets for cancer therapy.

    • Isaia Barbieri
    •  & Tony Kouzarides
  • Review Article |

    Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of rare neoplasms. This Review outlines our current understanding of the genomic defects and host environment characteristics that promote PTCL development with the aim of improving molecular stratification and targeted therapy for PTCLs.

    • Danilo Fiore
    • , Luca Vincenzo Cappelli
    • , Alessandro Broccoli
    • , Pier Luigi Zinzani
    • , Wing C. Chan
    •  & Giorgio Inghirami
  • Review Article |

    This Review outlines the recent advances in the creation of both combinatorial transgenic cancer models in zebrafish and zebrafish patient-derived xenograft models, and argues that these models have potential to be used as avatars for precision oncology.

    • Maurizio Fazio
    • , Julien Ablain
    • , Yan Chuan
    • , David M. Langenau
    •  & Leonard I. Zon
  • Review Article |

    This Review focuses on the role of tumour cell-autonomous signalling after radiotherapy. It describes how radiotherapy, through its immunomodulating effects, might be combined with immune checkpoint inhibitors and other immunotherapies and how DNA damage response inhibitors in combination with radiotherapy may be used to further augment this approach.

    • Martin McLaughlin
    • , Emmanuel C. Patin
    • , Malin Pedersen
    • , Anna Wilkins
    • , Magnus T. Dillon
    • , Alan A. Melcher
    •  & Kevin J. Harrington
  • Review Article |

    Recent single-cell RNA-sequencing studies have revealed a range of intratumoural T cell states, both within and between patients. This Review outlines the CD8+ T cell states that have been identified in human tumours and the potential roles they play in tumour control as well as how they are influenced by immune checkpoint blockade.

    • Anne M. van der Leun
    • , Daniela S. Thommen
    •  & Ton N. Schumacher
  • Review Article |

    This Review discusses the role that nerves play in the initiation and progression of cancers, focusing on the evidence that tumours may reactivate nerve-mediated developmental and regenerative pathways to promote their own growth and survival.

    • Ali H. Zahalka
    •  & Paul S. Frenette
  • Review Article |

    This Review summarizes the epidemiology literature linking data-driven and investigator-defined dietary patterns to cancer risk, providing expert appraisal of new developments in the field and highlighting both emerging mechanistic insights and key areas for future research.

    • Susan E. Steck
    •  & E. Angela Murphy
  • Review Article |

    The majority of cancers arise in individuals over the age of 60. This Review discusses how ageing tissues through changes in the extracellular matrix as well as in the functions of fibroblasts and immune cells can impact tumour initiation, progression and response to therapy.

    • Mitchell Fane
    •  & Ashani T. Weeraratna
  • Review Article |

    This Review discusses recent genomic, epigenomic, transcriptomic and proteomic profiling studies of human medulloblastoma that have advanced our understanding of its disease subgroups. These efforts have provided new insights into the diverse biology of medulloblastomas that will hopefully lead to improved diagnosis and therapy.

    • Volker Hovestadt
    • , Olivier Ayrault
    • , Fredrik J. Swartling
    • , Giles W. Robinson
    • , Stefan M. Pfister
    •  & Paul A. Northcott
  • Review Article |

    This Review discusses how advances in our understanding of the immune system within the brain have implications for the successful implementation of immunotherapy to treat brain tumours, despite challenges such as effective delivery, target specificity and intratumour heterogeneity.

    • John H. Sampson
    • , Michael D. Gunn
    • , Peter E. Fecci
    •  & David M. Ashley
  • Review Article |

    This Review discusses the role of bodily fluids and their underlying forces and imposed stresses in metastasis, highlighting the contributions of fluid mechanics to tumour cell intravasation, intravascular arrest and extravasation as well as to dissemination of tumour-derived factors.

    • Gautier Follain
    • , David Herrmann
    • , Sébastien Harlepp
    • , Vincent Hyenne
    • , Naël Osmani
    • , Sean C. Warren
    • , Paul Timpson
    •  & Jacky G. Goetz
  • Review Article |

    This Review discusses the PI3K–AKT signalling network and its control of cancer cell metabolism through both direct and indirect regulation of nutrient transport and metabolic enzymes, thereby connecting oncogenic signalling and metabolic reprogramming to support cancer cell survival and proliferation.

    • Gerta Hoxhaj
    •  & Brendan D. Manning
  • Review Article |

    This Review discusses the complex and context-dependent role of the complement system in cancer, highlighting the opposing effects of complement activation in both promoting and restraining tumour progression. A novel analysis of publicly available transcriptomic data to provide an overview of the prognostic value of complement gene expression in cancer is also included.

    • Lubka T. Roumenina
    • , Marie V. Daugan
    • , Florent Petitprez
    • , Catherine Sautès-Fridman
    •  & Wolf Herman Fridman
  • Review Article |

    To date, studies investigating mechanisms of therapy resistance have primarily focused on tumour-intrinsic changes, yet it is now clear that host responses to different cancer therapies can contribute to tumour regrowth, spread and resistance to therapy. This Review discusses the recent advances in understanding host-mediated pro-tumorigenic responses to cancer therapy, with an emphasis on therapy-induced immunological, angiogenic and metastatic effects.

    • Yuval Shaked
  • Review Article |

    This Review discusses the structure and function of the blood–brain barrier (BBB) and how brain tumours and brain metastases compromise BBB integrity. It also discusses the challenges the BBB poses for cancer therapy and how these might be overcome.

    • Costas D. Arvanitis
    • , Gino B. Ferraro
    •  & Rakesh K. Jain
  • Review Article |

    The research autopsy is an underused approach to investigate fundamental questions in cancer biology. This Review discusses the rationale for using research autopsies in cancer research, highlighting how this approach has improved knowledge of cancer biology and its tremendous potential to inform future precision medicine strategies.

    • Christine A. Iacobuzio-Donahue
    • , Chelsea Michael
    • , Priscilla Baez
    • , Rajya Kappagantula
    • , Jody E. Hooper
    •  & Travis J. Hollman
  • Review Article |

    Methionine uptake and metabolism contributes to cancer pathogenesis through functions in methylation reactions and one-carbon metabolism. This Review discusses methionine metabolism in the context of nutrition and the potential of targeting methionine metabolism in cancer through dietary or pharmacological intervention.

    • Sydney M. Sanderson
    • , Xia Gao
    • , Ziwei Dai
    •  & Jason W. Locasale
  • Review Article |

    Previous nanomedicine approaches have attempted to concentrate the action of cytotoxic therapies at tumours, generally with limited success. This Review discusses how the field is evolving to use nanoparticles and biomaterials to program the location, pharmacokinetics and co-delivery of immunotherapies, eliciting responses that cannot be achieved upon administration of such compounds in solution.

    • Michael S. Goldberg
  • Review Article |

    Innate immune checkpoints, including those regulating tumour detection and phagocytosis, have emerged as potential cancer immunotherapy targets. This Review discusses the role of phagocytosis checkpoints in cancer immune evasion, highlighting the preclinical and early clinical evidence supporting phagocytosis checkpoint blockade.

    • Mingye Feng
    • , Wen Jiang
    • , Betty Y. S. Kim
    • , Cheng Cheng Zhang
    • , Yang-Xin Fu
    •  & Irving L. Weissman
  • Review Article |

    Human germ cell tumours are a heterogeneous group of neoplasms that occur in the gonads and extragonadal sites along the midline of the body. This Review outlines a developmental pathogenetic model for the origin of all germ cell tumours, which is based on the unscheduled reprogramming of cells of the early embryo and germ line.

    • J. Wolter Oosterhuis
    •  & Leendert H. J. Looijenga
  • Review Article |

    Co-occurring genomic alterations contribute to the heterogeneity of driver oncogene-defined non-small-cell lung cancer subgroups. This Review discusses the effects of co-mutations on the pathogenesis, biology, microenvironmental interactions and therapeutic vulnerabilities of non-small-cell lung cancer.

    • Ferdinandos Skoulidis
    •  & John V. Heymach
  • Review Article |

    Endometrial cancer is histologically and molecularly complex, and effective clinical strategies for aggressive forms of the disease are needed. This Review discusses the identification and potential use of molecular features of endometrial cancer for early detection, treatment and risk stratification.

    • Mary Ellen Urick
    •  & Daphne W. Bell
  • Review Article |

    Paediatric solid tumours are known to be divergent from adult malignancies. This Review describes the molecular landscape of paediatric solid tumours, the therapeutic vulnerabilities that can be targeted and the preclinical models available to test the efficacy of investigational drugs with a view to accelerating translational progress.

    • David T. W. Jones
    • , Ana Banito
    • , Thomas G. P. Grünewald
    • , Michelle Haber
    • , Natalie Jäger
    • , Marcel Kool
    • , Till Milde
    • , Jan J. Molenaar
    • , Arash Nabbi
    • , Trevor J. Pugh
    • , Gudrun Schleiermacher
    • , Malcolm A. Smith
    • , Frank Westermann
    •  & Stefan M. Pfister
  • Review Article |

    The transcriptional activators YAP and TAZ have been discussed mainly for their cell-autonomous functions in cancer. Recent studies suggest their emerging roles in orchestrating tumour–stroma interactions, acting as a signalling hub, as discussed in this Review article.

    • Francesca Zanconato
    • , Michelangelo Cordenonsi
    •  & Stefano Piccolo
  • Review Article |

    This Review discusses the diverse effects of senescence and the senescence-associated secretory phenotype (SASP) on tumour growth, focusing on the functional and sometimes opposing outputs of the SASP in stromal cells and incipient tumour cells.

    • Douglas V. Faget
    • , Qihao Ren
    •  & Sheila A. Stewart
  • Review Article |

    Therapeutic strategies in malignant melanoma are challenged by resistance mechanisms that are based on phenotype plasticity. This Review discusses different phenotypes in melanoma, how they are controlled and how phenotype plasticity contributes to melanoma progression and therapy resistance.

    • Imanol Arozarena
    •  & Claudia Wellbrock
  • Review Article |

    This Review discusses the rapidly accumulating preclinical evidence in support of antitumour, but also of some pro-tumour, roles for γδ T cells in cancer progression. It also outlines the potential for manipulating their functions for use as an unconventional form of cancer immunotherapy.

    • Bruno Silva-Santos
    • , Sofia Mensurado
    •  & Seth B. Coffelt
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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