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    KRAS: reasons for optimism in lung cancer.

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    Authors
    Lindsay, Colin R
    Jamal-Hanjani, M
    Forster, M
    Blackhall, Fiona H
    Affiliation
    Division of Molecular and Clinical Cancer Sciences, University of Manchester, Manchester, UK
    Issue Date
    2018-06-09
    
    Metadata
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    Abstract
    Despite being the most frequent gain-of-function genetic alteration in human cancer, KRAS mutation has to date offered only limited potential as a prognostic and predictive biomarker. Results from the phase III SELECT-1 trial in non-small cell lung cancer (NSCLC) recently added to a number of historical and more contemporary disappointments in targeting KRAS mutant disease, including farnesyl transferase inhibition and synthetic lethality partners such as STK33. This narrative review uses the context of these previous failures to demonstrate how the knowledge gained from these experiences can be used as a platform for exciting advances in NSCLC on the horizon. It now seems clear that mutational subtype (most commonly G12C) of individual mutations is of greater relevance than the categorical evaluation of KRAS mutation presence or otherwise. A number of direct small molecules targeted to these subtypes are in development and have shown promising biological activity, with some in the late stages of preclinical validation.
    Citation
    KRAS: reasons for optimism in lung cancer. 2018, 99: 20-27 Eur J Cancer
    Journal
    European Journal of Cancer
    URI
    http://hdl.handle.net/10541/621087
    DOI
    10.1016/j.ejca.2018.05.001
    PubMed ID
    29894909
    Type
    Article
    Language
    en
    ISSN
    1879-0852
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ejca.2018.05.001
    Scopus Count
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