Genetics articles within Nature Reviews Clinical Oncology

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  • Review Article |

    Lung cancer is a disease typically associated with tobacco smoking; however, lung cancer in individuals who have never smoked (LCINS) is estimated to be the fifth most common cause of cancer-related deaths globally. Moreover, smoking rates are declining around the world and therefore LCINS is likely to increase as a proportion of all lung cancers over time. Thus, understanding the aetiology and features of LCINS is increasingly important. Herein, the authors review the emerging data on the epidemiology, clinical characteristics and molecular features of LCINS as well as the genetic and environmental risk factors for this disease. They also summarize the unique diagnostic and management paradigms of LCINS.

    • Jaclyn LoPiccolo
    • , Alexander Gusev
    •  & Pasi A. Jänne

  • Review Article |

    Although radiotherapy affects multiple cellular pathways, treatments are generally planned with the assumption that all tumours respond similarly to radiation. The authors of this Review summarize the effect of various pathways activated by radiotherapy on tumour responses to radiotherapy and present the current knowledge on genomic classifiers designed to inform treatment decisions.

    • James M. Price
    • , Asmithaa Prabhakaran
    •  & Catharine M. L. West

  • Review Article |

    Multiple myeloma and its precursor stages, monoclonal gammopathy of undetermined significance and smouldering multiple myeloma, have a considerable degree of genetic heterogeneity. The authors of this Review discuss how single-cell studies in these individuals are enabling the mutational and phenotypic characterization of cells within the bone marrow tumour, immune microenvironment and peripheral blood to eventually guide early diagnosis, risk stratification and treatment strategies.

    • Ankit K. Dutta
    • , Jean-Baptiste Alberge
    •  & Irene M. Ghobrial

  • News & Views |

    The identification of individuals carrying cancer susceptibility genetic variants could be improved by peridiagnostic cancer genetic testing and cascade testing of the relatives of patients diagnosed with cancer. Herein we discuss two studies that highlight the importance of active involvement of the medical team, both in informing the relatives and offering pre-test telephone genetic counselling.

    • Nora Pashayan
    •  & Clare Turnbull

  • News & Views |

    The identification of biomarkers and the development of genomics-based assays predictive of outcomes following radiotherapy, in an effort to help guide the treatment of patients with cancer, is an area of increasing research interest. Here, we discuss the validity of one such classifier, ARTIC, in the context of complementary genomic approaches designed to predict both tumour response and the susceptibility of nonmalignant tissues to toxicities resulting from radiotherapy.

    • David Azria
    •  & Barry S. Rosenstein

  • 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
    •  & David M. Thomas

  • Review Article |

    CRISPR systems have enabled important advances in cancer research by accelerating the development of study models or as a tool in genetic screening studies to discover and validate therapeutic targets. The authors of this Review discuss these applications and new potential uses, such as cancer detection and development of anticancer therapies.

    • Hao Yin
    • , Wen Xue
    •  & Daniel G. Anderson

  • News & Views |

    In a cohort of 100 patients with neuroendocrine cancer, the use of NETest enabled earlier prediction of tumour progression and resulted in a reduction in the frequency of follow-up procedures. These outcomes are exciting and promising, but limited in value by the heterogeneity of the study cohort and by suboptimal assay sensitivity and specificity.

    • Guido Rindi
    •  & Bertram Wiedenmann

  • Review Article |

    FGFR alterations can be detected in a small subset of many different cancer types. Inspired by the successes with other targeted therapies, preliminary attempts to target FGFR-altered cancers have been hampered by low response rates and acquired resistance. In this Review, the author describes the development of FGFR inhibitors thus far, and provides guidance on future research priorities.

    • Masaru Katoh

  • News & Views |

    Comprehensive molecular characterization of infant medulloblastoma has uncovered the high degree of heterogeneity of this disease. Recent results from the SJYC07 study elegantly reveal that risk stratification can be improved if DNA methylation profiling data are incorporated into clinicopathological criteria. Importantly, the delineation of disease subgroups potentially has major clinical implications.

    • Marc Remke
    •  & Vijay Ramaswamy

  • Review Article |

    The multiple myelomas (MMs) are heterogeneous malignancies that are nearly always associated with chromosomal abnormalities, which can be considered either primary or secondary abnormalities. The classification of MM according to the underlying primary cytogenetic abnormality might enable the development of better treatment strategies. The authors describe treatment approaches that consider the current standard of care for patients with MM along with recommendations for certain subgroups of patients.

    • Shaji K. Kumar
    •  & S. Vincent Rajkumar

  • Comment |

    According to the paradigm of precision medicine, the administration of agents targeting the molecular alteration detected in a particular patient’s tumour reduces uncertainty in the clinical management of that patient. We describe how approaches to precision medicine can lead, paradoxically, to increased levels of uncertainty. We offer recommendations for how physicians can better navigate new uncertainties in precision medicine.

    • Jonathan Kimmelman
    •  & Ian Tannock

  • Review Article |

    Patients with sarcomas have historically been treated with surgery and/or chemotherapy, although the outcomes achieved with these approaches, especially in advanced-stage disease, are often disappointing. In this Review, the authors describe the opportunities created by selective use of targeted therapies on the basis of the biological characteristics of individual tumours.

    • Armelle Dufresne
    • , Mehdi Brahmi
    •  & Jean-Yves Blay

  • Review Article |

    Developments in genomic sequencing technologies have enabled increasing amounts of information on the genomes of individual cancers to be revealed. At the same time, increasing numbers of therapies targeting specific genomic alterations are being made available, necessitating the use of genomics to diagnose and treat patients with cancer. In this Review, the authors describe the emerging clinical relevance of genomics in oncology, in addition to the many challenges that currently preclude routine clinical use.

    • Michael F. Berger
    •  & Elaine R. Mardis

  • Review Article |

    The safety of elective exogenous hormonal exposure among breast cancer survivors or women at high risk of having the disease has been debated for decades. Herein, the authors discuss the available data and present clinical recommendations regarding four areas of potential exogenous exposure to hormones: hormonal contraception; systemic hormone-replacement therapy; localized hormone-replacement therapy; and hormonal manipulation for fertility preservation or enhancement. Further research is needed to improve patient management in the future.

    • Ines Vaz-Luis
    •  & Ann H. Partridge

  • Review Article |

    Aberrant chromosomal architecture is one of the most common features of cancer and can often lead to chromosomal instability (CIN). In this Review, the authors describe the role of CIN in the development and progression of cancer and the potential to target the therapeutic vulnerabilities created by this process.

    • Laurent Sansregret
    • , Bart Vanhaesebroeck
    •  & Charles Swanton

  • News & Views |

    Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease for which treatment has, historically, lagged behind that of other solid tumour types. A more detailed understanding of the biology of individual tumours, and the identification of molecular features providing prognostic and predictive information is key to the application of personalized care for patients with MIBC. The publication of a study of 412 samples now provides such data.

    • Carolyn D. Hurst
    •  & Margaret A. Knowles

  • Research Highlight |

    • Diana Romero

  • Review Article |

    Radiomics is the high-throughput mining of quantitative image features from standard-of-care medical imaging to enable data to be extracted and applied within clinical-decision support systems. The process of radiomics is described and its pitfalls, challenges, opportunities, and capacity to improve clinical decision making. The radiomics field requires standardized evaluation of scientific findings and their clinical relevance. This review provides guidance for investigations to meet this urgent need in the field of radiomics.

    • Philippe Lambin
    • , Ralph T.H. Leijenaar
    •  & Sean Walsh

  • News & Views |

    Important biological questions can be addressed by interrogating the transcriptomes of cancer cells. In a recently published landmark study, Giustacchini and collaborators used a single-cell approach to analyse mRNA of cancer cells derived from patients with chronic myeloid leukaemia. Herein, we discuss how this approach could be used to address relevant clinical questions.

    • Sam Behjati
    •  & Muzlifah Haniffa

  • Review Article |

    Patients with early stage breast cancer have traditionally been assigned adjuvant systemic therapies on the basis of the clinical and histological characteristics of their disease. However, this approach often leads to overtreatment. In this Review, the authors describe the use of gene-expression signatures, some of which are already in clinical use, for determining the risks of recurrence and progression, and the most appropriate form of adjuvant therapy.

    • Maryann Kwa
    • , Andreas Makris
    •  & Francisco J. Esteva

  • News & Views |

    Fraser and colleagues describe the whole-genome sequencing (WGS) profiles of over 200 localized intermediate-risk prostate cancers. WGS has been widely used in research but not, thus far, in clinical settings. Herein, we consider the possible use of WGS in the field of precision oncology.

    • Marcin Imielinski
    •  & Mark A. Rubin

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