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    Understanding EGFR heterogeneity in lung cancer

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    Author
    Passaro, Antonio
    Malapelle, Umberto
    Del Re, Marzia
    Attili, Ilaria
    Russo, Alessandro
    Guerini-Rocco, Elena
    Fumagalli, Caterina
    Pisapia, Pasquale
    Pepe, Francesco
    De Luca, Caterina
    Cucchiara, Federico
    Troncone, Giancarlo
    Danesi, Romano
    Spaggiari, Lorenzo
    De Marinis, Filippo
    Rolfo, Christian
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    Date
    2020-10-16
    Journal
    ESMO open
    Publisher
    BMJ Publishing Group
    Type
    Article
    Other
    
    Metadata
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    See at
    https://doi.org/10.1136/esmoopen-2020-000919
    Abstract
    The advances in understanding the inherited biological mechanisms of non-small cell lung cancer harbouring epidermal growth factor receptor (EGFR) mutations led to a significant improvement in the outcomes of patients treated with EGFR tyrosine kinase inhibitors. Despite these clinically impressive results, clinical results are not always uniform, suggesting the need for deepening the molecular heterogeneity of this molecularly defined subgroup of patients beyond the clinical and biological surface. The availability of tissue and blood-based tumour genotyping allows us to improve the understanding of molecular and genetic intratumor heterogeneity, driving the measurement of clonal evaluation in patients with lung cancer carrying EGFR mutations. Genetic diversification, clonal expansion and selection are highly variable patterns of genetic diversity, resulting in different biological entities, also a prerequisite for Darwinian selection and therapeutic failure. Such emerging pieces of evidence on the genetic diversity, including adaptive and immunomodulated aspects, provide further evidence for the role of the tumour microenvironment (TME) in drug-resistance and immune-mediated mechanisms. Matching in daily clinical practice, the detailed genomic profile of lung cancer disease and tracking the clonal evolution could be the way to individualise the further target treatments in EGFR-positive disease. Characterising the tumour and immune microenvironment during the time of the cancer evaluation could be the way forward for the qualitative leap needed from bench to bedside. Such a daring approach, aiming at personalising treatment selection in order to exploit the TME properties and weaken tumour adaptivity, should be integrated into clinical trial design to optimise patient outcome.
    Rights/Terms
    © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.
    Keyword
    EGFR
    NSCLC
    heterogeneity
    mutations
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/13994
    ae974a485f413a2113503eed53cd6c53
    10.1136/esmoopen-2020-000919
    Scopus Count
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    UMB Open Access Articles 2020

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