Lung cancer articles within Nature Reviews Clinical Oncology

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  • Review Article |

    The receptor-tyrosine kinase RET has been identified as a potentially actionable driver of oncogenesis. Several multikinase inhibitors with activity against RET have been explored in the clinic, but have only modest efficacy in patients with thyroid cancers, mostly in those withRET mutations, or RET-rearranged lung cancers. Herein, the authors outline the aberrations in RET that contribute to tumorigenesis, review the current clinical data for inhibitors of this kinase, and discuss whether the limited clinical success achieved with these agents to date is attributable to the intractability of RET as a drug target or the lack of highly specific RET inhibitors.

    • Alexander Drilon
    • , Zishuo I. Hu
    •  & Daniel S. W. Tan

  • Review Article |

    The onset of acquired resistance to treatment is virtually inevitable in patients with solid tumours. In this Review, the authors describe the role of tumour heterogeneity in the development of acquired resistance, potential treatment strategies that take into account the heterogeneity of patient's tumours, and how a better understanding of tumour heterogeneity might improve the outcomes of patients.

    • Ibiayi Dagogo-Jack
    •  & Alice T. Shaw

  • Review Article |

    For three decades, the treatment of small-cell lung cancer (SCLC) has remained essentially unchanged, and patient outcomes remain dismal. In the past 5 years, however, advances in our understanding of the disease, at the molecular level, have resulted in the development of new therapeutic strategies, encompassing immunotherapies and novel molecularly targeted agents. Herein, authors review the breakthroughs that hold the promise to improve SCLC outcomes.

    • Joshua K. Sabari
    • , Benjamin H. Lok
    •  & Charles M. Rudin

  • Year in Review |

    In 2016, the pace of biological insights into small-cell lung cancer (SCLC) was reflected in new treatment approaches that have suggested meaningful clinical benefit to patients. We focus on three highlights of 2016: preclinical studies defining NFIB as a putative driver of metastasis, and two clinical studies; one that assessed the efficacy of an agent targeting the Notch ligand DLL3, and the other that explored T-cell checkpoint-blockade therapies targeting PD-1 and CTLA-4.

    • Charles M. Rudin
    •  & John T. Poirier

  • News & Views |

    Most patients with cancer who develop brain metastases have a very poor prognosis, especially those with brain metastases from non-small-cell lung cancer. The short life-expectancy of these patients, which is typically measured in weeks or a few months, raises an important question: do they benefit from whole-brain radiotherapy, or are they appropriately treated with best supportive care alone? A recent randomized trial sought to answer this question.

    • Dirk Rades
    •  & Steven E. Schild

  • News & Views |

    Eaton et al. report a very strong association between institutional clinical trial accrual volume and the survival of patients with stage III NSCLC. The observed volume effect might have been exaggerated by artefact. More work is required to quantify the volume effect and understand its causes, before rushing to centralize care.

    • William J. Mackillop
    •  & Christopher M. Booth

  • News & Views |

    The use of programmed cell-death protein 1 (PD-1) inhibitors has become the standard-of-care approach for patients with advanced-stage, previously treated non-small-cell lung cancer. The inevitable adoption of these agents in the first-line setting is rapidly approaching, but the optimal strategy remains unclear. Two published clinical trial reports, examining different approaches, help to frame this question.

    • Stephen V. Liu
    •  & Giuseppe Giaccone

  • News & Views |

    Annual thoracic CT screening is currently recommended for individuals deemed to be at high risk of developing lung cancer; however, Patz and co-workers now raise the very important question of choosing the optimal interval between screening exams, in order to balance the potential benefits and harms associated with each round of CT. Herein, we present important considerations for determining such intervals.

    • David Yankelevitz
    •  & Claudia Henschke

  • News & Views |

    Analysis of circulating tumour DNA (ctDNA) in blood samples provides a surrogate form of tumour biopsy (liquid biopsy) for determining EGFR and KRAS mutation status in patients with advanced-stage non-small-cell lung cancer. This approach obviates the need for a repeat biopsy, especially for the EGFR T790M mutation, which confers resistance to EGFR inhibition.

    • Rafael Rosell
    •  & Niki Karachaliou

  • Year in Review |

    In 2015, advances in immunotherapy for metastatic melanoma have come to fruition, with phase III data supporting the combination of ipilimumab and nivolumab as first-line therapy. Understanding the mechanisms involved in an effective antitumour immune response are now key to further advances. Several studies published in 2015 have increased our understanding of the complex relationships that exist between our immune system and malignancy.

    • Elizabeth I. Buchbinder
    •  & F. Stephen Hodi

  • Year in Review |

    Lung-cancer treatment paradigms continue to advance as we exploit our growing understanding of the genetic basis of both tumorigenesis and therapy resistance. Moreover, ongoing developments with targeted therapies are improving patient outcomes, with two new drugs approved in 2015 for non-small-cell lung cancer and many others showing promise.

    • Egbert F. Smit
    •  & Paul Baas

  • News & Views |

    In the RADIANT study, no difference in disease-free survival was observed for patients with non-small-cell lung cancer (NSCLC) treated with erlotinib versus placebo in the adjuvant setting. Further biomarker studies are awaited to determine whether patients with NSCLC can benefit from adjuvant therapy with tyrosine kinase inhibitors.

    • Fred R. Hirsch
    •  & Paul A. Bunn Jr

  • Review Article |

    The use of traditional Euclidean geometry can present challenges for analysis of image characteristics, particular those of extremely complex biological structures, obtained by medical and scientific imaging modalities. Fractal geometry is a potentially complementary mathematical approach that enables efficient estimation of geometrical complexity, and the irregularity of shapes and patterns. This Review introduces the concept of fractals and fractal geometry, and describes how analysis of fractal (non-integer) dimension and associated measurements, such as lacunarity (texture), can be performed and applied to the analysis of cancer. The authors discuss how fractal analysis might provide information on many diverse biological structures relevant to the natural history of lung cancer, which might prove useful for the diagnosis and management of this disease.

    • Frances E. Lennon
    • , Gianguido C. Cianci
    •  & Ravi Salgia

  • Review Article |

    The recognition of non-small-cell lung cancer (NSCLC) as a heterogeneous disease and ongoing efforts to characterize disease subtypes based on genotype and histology have resulted in dramatic improvements in outcomes for select patient subgroups. However, many challenges remain, not least acquired therapeutic resistance and the related issue of how to best use the available therapies. In this Review, the authors provide an overview of the key developments in NSCLC therapy, describe efforts to tackle therapeutic resistance, and discuss potential strategies to further optimize patient outcomes by stratifying treatments according to particular disease subtypes.

    • Anish Thomas
    • , Stephen V. Liu
    •  & Giuseppe Giaccone

  • Review Article |

    PET has evolved from a purely diagnostic imaging technique to a multifunctional modality that can provide diverse information of relevance to oncological management. This modality might offer the potential to improve patient care and outcomes by enabling better disease characterization, treatment-response monitoring, and follow-up assessment. Herein, the authors discuss the data supporting the use of PET in personalizing the clinical management of patients with locally advanced and metastatic non-small-cell lung cancer.

    • Willem Grootjans
    • , Lioe-Fee de Geus-Oei
    •  & Johan Bussink

  • News & Views |

    Owing to the institution of annual low-dose CT for lung cancer screening in the USA, the presumed increase in detection of early stage lung cancers elicits many questions about so-called 'grey areas' of the management of this disease that have been inadequately addressed to date. Herein, important and potentially difficult ambiguous cases that oncologists might come across are discussed.

    • Vivek Verma

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