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    Small-cell lung cancer

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    Authors
    Rudin, C. M.
    Brambilla, E.
    Faivre-Finn, Corinne
    Sage, J.
    Affiliation
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Issue Date
    2021
    
    Metadata
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    Abstract
    Small-cell lung cancer (SCLC) represents about 15% of all lung cancers and is marked by an exceptionally high proliferative rate, strong predilection for early metastasis and poor prognosis. SCLC is strongly associated with exposure to tobacco carcinogens. Most patients have metastatic disease at diagnosis, with only one-third having earlier-stage disease that is amenable to potentially curative multimodality therapy. Genomic profiling of SCLC reveals extensive chromosomal rearrangements and a high mutation burden, almost always including functional inactivation of the tumour suppressor genes TP53 and RB1. Analyses of both human SCLC and murine models have defined subtypes of disease based on the relative expression of dominant transcriptional regulators and have also revealed substantial intratumoural heterogeneity. Aspects of this heterogeneity have been implicated in tumour evolution, metastasis and acquired therapeutic resistance. Although clinical progress in SCLC treatment has been notoriously slow, a better understanding of the biology of disease has uncovered novel vulnerabilities that might be amenable to targeted therapeutic approaches. The recent introduction of immune checkpoint blockade into the treatment of patients with SCLC is offering new hope, with a small subset of patients deriving prolonged benefit. Strategies to direct targeted therapies to those patients who are most likely to respond and to extend the durable benefit of effective antitumour immunity to a greater fraction of patients are urgently needed and are now being actively explored.
    Citation
    Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers. 2021;7(1):3.
    Journal
    Nature Reviews Disease Primers
    URI
    http://hdl.handle.net/10541/623793
    DOI
    10.1038/s41572-020-00235-0
    PubMed ID
    33446664
    Additional Links
    https://dx.doi.org/10.1038/s41572-020-00235-0
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41572-020-00235-0
    Scopus Count
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