Papers

Peer-reviewed
Sep, 2015

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

SCIENTIFIC REPORTS
  • Kenichi Suda
  • Isao Murakami
  • Kazuko Sakai
  • Hiroshi Mizuuchi
  • Shigeki Shimizu
  • Katsuaki Sato
  • Kenji Tomizawa
  • Shuta Tomida
  • Yasushi Yatabe
  • Kazuto Nishio
  • Tetsuya Mitsudomi
  • Display all

Volume
5
Number
First page
14447
Last page
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1038/srep14447
Publisher
NATURE PUBLISHING GROUP

Lung cancers often harbour a mutation in the epidermal growth factor receptor (EGFR) gene. Because proliferation and survival of lung cancers with EGFR 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 EGFR 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 EGFR T790M mutation. In particular, target sequencing revealed a TP53 P151S mutation in all pre-and post-treatment lesions. PTEN M264I mutation was identified only in a TKI-refractory lesion with SCLC transformation, while PIK3CA and RB1 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.

Link information
DOI
https://doi.org/10.1038/srep14447
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26400668
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000361657800001&DestApp=WOS_CPL
ID information
  • DOI : 10.1038/srep14447
  • ISSN : 2045-2322
  • Pubmed ID : 26400668
  • Web of Science ID : WOS:000361657800001

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