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Acquired resistance in oncogene-addicted non-small-cell lung cancer

    Claudio Sini

    *Author for correspondence:

    E-mail Address: audiosini@tiscali.it

    Medical Oncology, Ospedale Giovanni Paolo II, Olbia, Italy

    ,
    Alessandro Tuzi

    Medical Oncology, ASST-Settelaghi, Varese, Italy

    ,
    Giovanni Rossi

    Lung Unit, Ospedale Policlinico San Martino, Genova, Italy

    ,
    Alessandro Russo

    Medical Oncology Unit, AO Papardo & Department of Human Pathology, University of Messina, Messina, Italy

    Borsa Dottorati FSE XXXII Ciclo Unime, University of Messina, Messina, Italy

    &
    Aldo Pezzuto

    Cardiovascular & Thoracic Department, AOU Sant'Andrea, Sapienza – Università di Roma, Roma, Italy

    Published Online:https://doi.org/10.2217/fon-2018-0097

    The advance of tyrosine kinase inhibitors has profoundly changed the therapeutic algorithm of non-small-cell lung cancer in molecularly selected patients. However, benefit from these agents is often transient and usually most patients progress within 12 months from treatment. Novel and more potent and selective tyrosine kinase inhibitors have been developed to overcome acquired resistance; however, these agents are once again associated with only temporary benefit and patients frequently develop secondary resistance, a heterogeneous phenomenon that involves different molecular mechanisms simultaneously. The aim of our paper is to provide a comprehensive overview of the mechanisms of acquired resistance in oncogene-addicted non-small-cell lung cancer, focusing on the two most studied target, EGFR mutations and ALK translocation, and reviewing the main challenges in clinical practice.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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