Browse Articles

  • News & Views |

    In recent decades, cancer survival has improved dramatically, resulting in a growing population of cancer survivors with chronic health needs and disease risks. While large epidemiological studies are useful in tracking broad trends in health outcomes of cancer survivors, they lack the level of detail needed to inform the delivery of appropriate clinical care and optimal allocation of resources.

    • Eden R. Brauer
    •  & Patricia A. Ganz
  • Perspective |

    The oligometastatic paradigm challenges the prevailing view of metastasis as a disseminated process and proposes the existence of a spectrum of biological virulence within metastatic lesions. The authors present evidence for this heterogeneity and discuss how it affects the staging and treatment of patients with metastatic cancer.

    • Sean P. Pitroda
    •  & Ralph R. Weichselbaum
  • News & Views |

    Identification of factors predicting recurrence of breast cancer is a long-standing goal, ranging from classical clinicopathological factors through to immunohistochemical assays of receptor levels and, more recently, the expression levels of several genes. A new paper now explores novel expression markers, especially for late recurrence of oestrogen receptor-positive breast cancer.

    • Jack Cuzick
  • Review Article |

    Immune-checkpoint inhibitors (ICIs) have dramatically improved the survival of patients with certain forms of cancer; however, these agents also have adverse effects that are often quite different to those of more traditional cancer therapies. In this Review, the authors describe the epidemiology, treatment and management of the various immune-related adverse events that can occur in patients receiving ICIs.

    • Filipe Martins
    • , Latifyan Sofiya
    • , Gerasimos P. Sykiotis
    • , Faiza Lamine
    • , Michel Maillard
    • , Montserrat Fraga
    • , Keyvan Shabafrouz
    • , Camillo Ribi
    • , Anne Cairoli
    • , Yan Guex-Crosier
    • , Thierry Kuntzer
    • , Olivier Michielin
    • , Solange Peters
    • , Georges Coukos
    • , Francois Spertini
    • , John A. Thompson
    •  & Michel Obeid
  • Comment |

    Breast oncologists are intimately familiar with managing treatment-related adverse events of endocrine, cytotoxic and targeted therapies, but the approval of immune-checkpoint inhibitors (ICIs) for metastatic triple-negative breast cancer (TNBC) poses new challenges. Herein, we discuss the safety of ICIs in metastatic TNBC, with an emphasis on immune-related adverse events.

    • Nina D’Abreo
    •  & Sylvia Adams
  • Review Article |

    The therapeutic options currently available for patients with metastatic renal cell carcinoma (RCC) include immune-checkpoint inhibitors, novel targeted agents and combination strategies, and thus optimal patient selection and treatment sequencing are important. The authors review relevant aspects of the molecular biology of metastatic RCC, with an emphasis on biomarkers, and suggest tailored algorithms to individualize and guide treatment approaches

    • Ritesh R. Kotecha
    • , Robert J. Motzer
    •  & Martin H. Voss
  • Review Article |

    The metabolic conditions in tumours can result in phenotypic reprogramming of non-tumour cells, including immune cells, in the tumour microenvironment. This Review provides an overview of the pathways of cancer metabolism that intersect with immunometabolism, typically resulting in immunosuppression, with a focus on how these metabolic pathways could be targeted in order to enhance anticancer immunity and immunotherapy.

    • Xiaoyun Li
    • , Mathias Wenes
    • , Pedro Romero
    • , Stanley Ching-Cheng Huang
    • , Sarah-Maria Fendt
    •  & Ping-Chih Ho
  • News & Views |

    Glioblastoma remains essentially incurable, and new therapeutic approaches are urgently needed. Now, the findings of three serial tissue-based studies suggest that immune-checkpoint inhibition can modify the glioblastoma microenvironment. Following these encouraging observations, the results of two phase III trials of immune-checkpoint inhibition in newly diagnosed glioblastoma, with larger cohorts of patients, are eagerly anticipated.

    • Michael Weller
    •  & Emilie Le Rhun
  • Review Article |

    Immunotherapy with immune-checkpoint inhibitors (ICIs) is a new pillar in the treatment of cancer but can a have range of immune-related adverse effects, including some rare neurological toxicities that constitute paraneoplastic neurological syndromes (PNSs). In this Review, the authors provide an overview of PNSs, the associations of these conditions with ICI therapy and recommendations for the prevention and management of ICI-associated PNSs.

    • Francesc Graus
    •  & Josep Dalmau
  • News & Views |

    Using the example of the recently reported phase III MAIA trial, we emphasize herein the requirement to dig deeper into trial designs and end points to determine their appropriateness for the questions at hand and to assess whether a benefit in terms of the primary end point — even if statistically significant and seemingly clinically meaningful — is sufficient to warrant a change in clinical practice.

    • Prashant Kapoor
    •  & S. Vincent Rajkumar
  • Review Article |

    The development of chimeric antigen receptor (CAR) T cell therapy is an important advance in the treatment of cancer. Herein, the authors outline the key limitations of CAR T cell therapy, with a focus on mechanisms of resistance, and discuss strategies to improve the efficacy and broaden the applicability of this promising therapeutic approach.

    • Nirali N. Shah
    •  & Terry J. Fry
  • Review Article |

    Patients with lymphoma typically receive chemotherapy as the first-line treatment. However, patients who fail to respond or develop relapsed disease often have poor outcomes. In this Review, the authors summarize the available data on therapeutics designed to modulate epigenetic changes, including DNA methylation and histone acetylation, in patients with lymphoma and describe the most promising directions of future research.

    • David Sermer
    • , Laura Pasqualucci
    • , Hans-Guido Wendel
    • , Ari Melnick
    •  & Anas Younes
  • News & Views |

    Inhibition of the NKG2A immune checkpoint restores natural killer cell and T cell effector function in preclinical cancer models. In addition, NKG2A blockade in combination with other therapeutic antibodies is showing encouraging responses in a subset of patients with metastatic colorectal or head and neck cancer. However, established biomarkers of response are lacking, and larger trials are needed to enable firm conclusions to be drawn about whether NKG2A inhibition complements existing immunotherapies.

    • Benjamin C. Creelan
    •  & Scott J. Antonia
  • Review Article |

    Despite much hope, anti-angiogenic agents have largely failed to achieve the promise demonstrated in preclinical models. In this Review, the authors discuss an alternative hypothesis — vessel co-option — that might explain many of these failures and describe the evidence for a role of this largely overlooked aspect of tumour biology.

    • Elizabeth A. Kuczynski
    • , Peter B. Vermeulen
    • , Francesco Pezzella
    • , Robert S. Kerbel
    •  & Andrew R. Reynolds
  • News & Views |

    Recently published data from the ZUMA-1 and JULIET trials suggest that CD19-directed chimeric antigen receptor (CAR) T cell therapy can provide durable remissions, with a low risk of relapse or progression, in 30–40% of patients with relapsed and/or refractory aggressive large B cell lymphoma. Two-year follow-up of the ZUMA-1 clinical trial has not revealed any unexpected toxicities, but further safety monitoring will be needed.

    • David G. Maloney
  • Review Article |

    In this Review, Pantel and Alix-Panabières provide an overview of approaches for the detection and characterization of minimal residual disease (MRD) using circulating tumour cells and circulating tumour DNA. They also discuss the clinical implications of such liquid biopsy approaches to MRD monitoring for the management of patients with cancer.

    • Klaus Pantel
    •  & Catherine Alix-Panabières
  • Review Article |

    The majority of genetically targeted approaches to cancer therapy focus on somatic mutations. However, evidence is accumulating in support of a role for germline genetic alterations in determining responsiveness to treatment. In this Review, the authors summarize the therapeutic potential of knowledge of the germline genome in patients with cancer.

    • Subotheni Thavaneswaran
    • , Emma Rath
    • , Kathy Tucker
    • , Anthony M. Joshua
    • , Dominique Hess
    • , Mark Pinese
    • , Mandy L. Ballinger
    •  & David M. Thomas
  • Comment |

    The approval of therapeutic agents that are tested in patients deemed ineligible for intensive or aggressive therapy is increasingly popular. This approach enables comparisons of novel therapies with less-aggressive agents, as well as data from nonrandomized studies to be used for market authorization. Herein, we discuss three mechanisms that could be adopted to avoid the temptation of applying this strategy excessively.

    • Rachel J. Cook
    • , Jennifer Gill
    •  & Vinay Prasad
  • Consensus Statement | | open

    Brain cancer encompasses a diverse range of complex malignancies, many of which are associated with a poor prognosis and require more effective treatments. In this Position Paper, an international panel of clinicians and laboratory-based scientists convened by Cancer Research UK identify and discuss seven challenges that must be overcome if we are to cure all patients with a brain tumour.

    • Kenneth Aldape
    • , Kevin M. Brindle
    • , Louis Chesler
    • , Rajesh Chopra
    • , Amar Gajjar
    • , Mark R. Gilbert
    • , Nicholas Gottardo
    • , David H. Gutmann
    • , Darren Hargrave
    • , Eric C. Holland
    • , David T. W. Jones
    • , Johanna A. Joyce
    • , Pamela Kearns
    • , Mark W. Kieran
    • , Ingo K. Mellinghoff
    • , Melinda Merchant
    • , Stefan M. Pfister
    • , Steven M. Pollard
    • , Vijay Ramaswamy
    • , Jeremy N. Rich
    • , Giles W. Robinson
    • , David H. Rowitch
    • , John H. Sampson
    • , Michael D. Taylor
    • , Paul Workman
    •  & Richard J. Gilbertson