Small cell lung cancer transformation and T790M mutation: complimentary roles in acquired resistance to kinase inhibitors in lung cancer

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書誌事項

公開日
2015-09-24
権利情報
  • https://creativecommons.org/licenses/by/4.0
  • https://creativecommons.org/licenses/by/4.0
DOI
  • 10.1038/srep14447
公開者
Springer Science and Business Media LLC

説明

<jats:title>Abstract</jats:title><jats:p>Lung cancers often harbour a mutation in the epidermal growth factor receptor (<jats:italic>EGFR</jats:italic>) gene. Because proliferation and survival of lung cancers with <jats:italic>EGFR</jats:italic> mutation solely depend on aberrant signalling from the mutated EGFR, these tumours often show dramatic responses to EGFR tyrosine kinase inhibitors (TKIs). However, acquiring resistance to these drugs is almost inevitable, thus a better understanding of the underlying resistance mechanisms is critical. Small cell lung cancer (SCLC) transformation is a relatively rare acquired resistance mechanism that has lately attracted considerable attention. In the present study, through an in-depth analysis of multiple EGFR-TKI refractory lesions obtained from an autopsy case, we observed a complementary relationship between SCLC transformation and <jats:italic>EGFR</jats:italic> T790M secondary mutation (resistance mutation). We also identified analogies and differences in genetic aberration between a TKI-refractory lesion with SCLC transformation and one with <jats:italic>EGFR</jats:italic> T790M mutation. In particular, target sequencing revealed a <jats:italic>TP53</jats:italic> P151S mutation in all pre- and post-treatment lesions. <jats:italic>PTEN</jats:italic> M264I mutation was identified only in a TKI-refractory lesion with SCLC transformation, while <jats:italic>PIK3CA</jats:italic> and <jats:italic>RB1</jats:italic> mutations were identified only in pre-treatment primary tumour samples. These results provide the groundwork for understanding acquired resistance to EGFR-TKIs via SCLC transformation.</jats:p>

収録刊行物

  • Scientific Reports

    Scientific Reports 5 (1), 14447-, 2015-09-24

    Springer Science and Business Media LLC

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