Acquired resistance to gefitinib: the contribution of mechanisms other than the T790M, MET, and HGF status.

Some types of somatic mutation of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) are associated with a significant clinical response to a tyrosine kinase inhibitor (TKI). However, most of the patients with this type of sensitive mutations in their tumor show acquired resistance during the TKI treatment. The mutations in exons 19-21 of the EGFR gene were examined in both the pre-treatment and the post-treatment gefitinib resistant tumors in 10 patients with lung adenocarcinoma. Eight patients were recurrent cases after surgery, and two patients were non-surgical cases whose tumor specimens were obtained from the metastatic lymph node and endobronchially invading tumor. In 10 patients, 5 patients had a deletion in exon 19 and another 5 did L858R mutation in exon 21 of EGFR in gefitinib pre-treatment tumors. The mutation status did not change in the gefitinib-resistant tumors. In 7 of 10 patients, the gefitinib-resistant tumors had a secondary T790M mutation, which was not detected in the gefitinib pre-treatment tumors. In one patient, only one of the 4 gefitinib-resistant tumors showed the T790M mutation. Neither other novel secondary mutations of EGFR nor the K-ras were observed in their gefitinib-resistant tumors. Neither MET gene amplification nor HGF were observed in their gefitinib-resistant tumors without T790M mutation. The T790M mutation in the EGFR is relatively common in the patients with acquired resistance to gefitinib. However, mechanisms other than T790M, MET, and HGF status are involved in resistance to gefitinib.

Onitsuka T ，Uramoto H ，Nose N ，Takenoyama M ，Hanagiri T ，Sugio K ，Yasumoto K ... -  《-》

Prognostic value of acquired resistance-related molecules in Japanese patients with NSCLC treated with an EGFR-TKI.

Uramoto H ，Yamada T ，Yano S ，Kondo N ，Hasegawa S ，Tanaka F ... -  《-》

Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib.

Kosaka T ，Yatabe Y ，Endoh H ，Yoshida K ，Hida T ，Tsuboi M ，Tada H ，Kuwano H ，Mitsudomi T ... -  《CLINICAL CANCER RESEARCH》

First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations.

Sequist LV ，Martins RG ，Spigel D ，Grunberg SM ，Spira A ，Jänne PA ，Joshi VA ，McCollum D ，Evans TL ，Muzikansky A ，Kuhlmann GL ，Han M ，Goldberg JS ，Settleman J ，Iafrate AJ ，Engelman JA ，Haber DA ，Johnson BE ，Lynch TJ ... -  《-》

Addition of S-1 to the epidermal growth factor receptor inhibitor gefitinib overcomes gefitinib resistance in non-small cell lung cancer cell lines with MET amplification.

Okabe T ，Okamoto I ，Tsukioka S ，Uchida J ，Hatashita E ，Yamada Y ，Yoshida T ，Nishio K ，Fukuoka M ，Jänne PA ，Nakagawa K ... -  《CLINICAL CANCER RESEARCH》