Latest Research

  • Review Article |

    CD19-specific chimeric antigen (CAR)-modified T cells are approved for patients with advanced-stage forms of certain B cell malignancies. However, a subset of patients will have anti-CAR immune responses, leading to a lack of CAR T cell persistence and a rapid loss of any antitumour efficacy. In this Review, the authors describe the extent of anti-CAR immune responses in patients and suggest measures that could be used to better monitor for these events. Additionally, they describe novel approaches to CAR T cell therapy that might reduce the risk of such responses in the future.

    • Dimitrios L. Wagner
    • , Enrico Fritsche
    •  & Mohamed Abou-el-Enein
  • Consensus Statement |

    In this Consensus Statement, members from five working groups or societies provide updated comprehensive recommendations to manage toxicities from cancer immunotherapies in children, adolescents and young adults. In their recommendations, they advocate for the adoption of age-based and discipline-specific management criteria, and call for an increased inclusion of young patients with cancer in clinical trials.

    • Dristhi Ragoonanan
    • , Sajad J. Khazal
    •  & Kris M. Mahadeo
  • Review Article |

    PD-L1 expression is currently the best available biomarker for the prediction of responsiveness to immune-checkpoint inhibitors. However, several immunohistochemical assays are now approved for clinical use in various settings, despite imperfect inter-assay concordance, with important implications for pathology services and, potentially, for clinical outcomes. In this Review, the authors compare the performance of the various FDA-approved PD-L1 assays, discuss the varying implications of PD-L1 expression across different tumour types and provide guidance on possible novel approaches that might optimize the clinical utility of PD-L1 as a biomarker.

    • Deborah Blythe Doroshow
    • , Sheena Bhalla
    •  & Fred R. Hirsch
  • Review Article |

    Antibody–drug conjugates (ADCs) constitute a unique class of anticancer agents with demonstrated clinical efficacy against several different cancer types. Herein, the authors discuss the design and mechanisms of action of ADCs and how these properties are reflected in the clinical activity and toxicity profiles of such agents. Potential strategies to overcome the limitations of ADCs and thereby maximize their therapeutic benefit for patients with cancer are also proposed.

    • Joshua Z. Drago
    • , Shanu Modi
    •  & Sarat Chandarlapaty
  • Review Article |

    Ferroptosis is an iron-dependent form of regulated cell death driven by excessive lipid peroxidation. Pharmacological agents, ionizing radiation and cytokines can induce ferroptosis and thus suppress tumour growth, but ferroptosis can also trigger inflammation-associated immunosuppression. The authors describe the key molecular mechanisms of ferroptosis, including crosstalk with tumour-associated signalling pathways, and discuss potential therapeutic applications of ferroptosis.

    • Xin Chen
    • , Rui Kang
    •  & Daolin Tang
  • Review Article |

    A host of additional toxicities and/or potential late effects of chimeric antigen receptor (CAR) T cell therapy beyond cytokine release syndrome (CRS) warrant further investigation. Herein, experts in paediatric cell therapy, supportive care and/or study of late effects from cancer and haematopoietic stem cell transplantation present six key focus research areas related to CAR T cell-related outcomes beyond CRS.

    • Haneen Shalabi
    • , Juliane Gust
    •  & Nirali N. Shah
  • Perspective |

    Liquid biopsy assays have the potential to revolutionize the diagnosis and management of cancer, and rapid progress is being made in the clinical translation of such assays. This Perspective outlines notable advances in the use of liquid biopsy technologies in the management of solid tumours, as well as future research avenues, clinical trial methodologies and implementation logistics for the eventual integration of liquid biopsy into the clinical workflow.

    • Michail Ignatiadis
    • , George W. Sledge
    •  & Stefanie S. Jeffrey
  • Review Article |

    Personalized neoantigen-based therapeutic vaccines hold promise as cancer immunotherapies. This Review provides an overview of the complex personalized neoantigen vaccine production process, vaccine-induced T cell responses and strategies to enhance these responses. Completed and ongoing clinical studies testing such vaccines are discussed, and considerations for future clinical investigation of this novel, individualized form of immunotherapy are outlined.

    • Eryn Blass
    •  & Patrick A. Ott
  • Review Article |

    Chronic inflammation can promote the development of various cancers. In this Review, the current clinical advances in ameliorating inflammation for the prevention or treatment of cancer are highlighted, and the experimental insights into the biological mechanisms supporting current and potential novel anti-inflammatory approaches to the management of cancer are discussed.

    • Jiajie Hou
    • , Michael Karin
    •  & Beicheng Sun
  • Review Article |

    Renal cell carcinomas (RCCs) are generally immunogenic, but only a subset of patients receiving currently approved immune-checkpoint inhibitors have long-term disease remission. In this Review, the authors provide a conceptual framework for developing novel immunotherapy approaches, including an overview of the most promising novel immune checkpoints and antigen-directed therapies, and highlighting the potential of these agents to further improve the outcomes in patients with RCC.

    • David A. Braun
    • , Ziad Bakouny
    •  & Toni K. Choueiri
  • Evidence-based Guidelines
    | Open Access

    Herein, the European Association of Neuro-Oncology (EANO) provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. These evidence-based guidelines incorporate major changes in diagnostic algorithms based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System as well as on evidence from recent large clinical trials.

    • Michael Weller
    • , Martin van den Bent
    •  & Wolfgang Wick
  • Perspective |

    The availability of ever more sensitive cell sorting and sequencing technologies has enabled the interrogation of tumour cell biology at the highest possible level of resolution — analysis of a single cell. In this Perspective, the authors describe the application of such approaches to the analysis of single tumour-associated immune cells and their potential for improving the outcomes in patients receiving anti-cancer immunotherapies.

    • Satyen H. Gohil
    • , J. Bryan Iorgulescu
    •  & Kenneth J. Livak
  • Perspective |

    The incidence of early-onset colorectal cancer (CRC) is increasing worldwide for reasons that are currently unclear. Herein, the authors review the current epidemiological, clinical, pathological and molecular understanding of early-onset CRC that occurs in patients ≥50 years of age, drawing contrasts with later-onset CRC. They also discuss future research strategies for improved understanding, prevention, early detection and clinical management of early-onset CRC.

    • Naohiko Akimoto
    • , Tomotaka Ugai
    •  & Shuji Ogino
  • Review Article |

    Nuclear import and export proteins, such as exportin 1(XPO1), regulate the transport of proteins and other molecules into and out of the nucleus, including several tumour suppressor proteins. The dysregulation of nuclear export can be observed in several types of haematological and solid tumours, providing a rationale for a novel form of targeted therapy. In this Review, the authors describe the development of XPO1 inhibitors, from basic research to clinical approval.

    • Asfar S. Azmi
    • , Mohammed H. Uddin
    •  & Ramzi M. Mohammad
  • Review Article |

    Despite the introduction of novel therapies, lung cancer remains the leading cause of cancer-related mortality worldwide. Randomized controlled trials of low-dose CT-based lung cancer screening in high-risk populations have shown a reduction in mortality. The authors of this Review discuss these studies and present the Screening Planning and Implementation RAtionale for Lung cancer (SPIRAL), a framework to define the scope of future implementation research on lung cancer screening.

    • Matthijs Oudkerk
    • , ShiYuan Liu
    •  & John K. Field
  • Review Article |

    Despite several major therapeutic advances, multiple myeloma (MM) remains largely incurable, indicating a need for novel therapies. Thus, considerable research interest exists in chimeric antigen receptor (CAR) T cells targeting BCMA, which is almost universally expressed on MM cells. In this Review, the authors describe the clinical experience with anti-BCMA CAR T cells and discuss several new directions of future research that might prolong the responses of patients receiving these therapies.

    • Lekha Mikkilineni
    •  & James N. Kochenderfer
  • Review Article |

    Technological advances have enabled the analysis of whole genomes, leading to the identification of causal factors that present new opportunities to prevent cancer. The authors of this Review discuss relevant findings in cancer genetics and genomics from the perspective of global cancer prevention and present a conceptual framework for the translation of such findings into clinical practice and evidence-based policies.

    • Ophira Ginsburg
    • , Patricia Ashton-Prolla
    •  & Paul Brennan
  • Review Article |

    Natural killer (NK) cells have an innate potential to kill cancerous cells and considerable effort is being focused on innovative approaches to leverage these cells for cancer therapy. Herein, the authors discuss the variety of NK cell-based therapies that are being developed for the treatment of diverse cancers and identify future avenues for NK cell therapy research.

    • Jacob A. Myers
    •  & Jeffrey S. Miller
  • Perspective |

    Genotyping is recommended for all patients with metastatic non-squamous non-small-cell lung cancers (NSCLC), both to enable patients to receive targeted therapies and to avoid therapies they are unlikely to benefit from. However, obtaining tumour biopsy material for genotyping is often challenging and is unfeasible in some patients, indicating the need to incorporate liquid biopsy approaches. In this Perspective, the authors provide guidance on how analysis of ctDNA from liquid biopsy samples in patients with metastatic NSCLC prior to first-line therapy has the potential to extend the benefits of genotyping to virtually all patients.

    • Charu Aggarwal
    • , Christian D. Rolfo
    •  & David R. Gandara