論文 - 詳細
| RRC ID | 69806 |
|---|---|
| 著者 | Katayama Y, Yamada T, Tokuda S, Okura N, Nishioka N, Morimoto K, Tanimura K, Morimoto Y, Iwasaku M, Horinaka M, Sakai T, Kita K, Yano S, Takayama K. |
| タイトル | Heterogeneity among tumors with acquired resistance to EGFR tyrosine kinase inhibitors harboring EGFR-T790M mutation in non-small cell lung cancer cells. |
| ジャーナル | Cancer Med |
| Abstract |
EGFR-T790M mutation is a major mechanism underlying acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) in lung cancer with mutated EGFR. However, differences in the biological characteristics of T790M tumors based on treatment regimens with each generation of EGFR-TKI are not fully understood. We established cell lines with acquired resistance harboring EGFR-T790M mutation derived from xenograft tumors treated with each generation of EGFR-TKI and examined their biological characteristics with respect to third-generation EGFR-TKI osimertinib sensitivity. Second-generation EGFR-TKI dacomitinib-resistant cells with T790M-exhibited higher sensitivity to osimertinib than first-generation EGFR-TKI gefitinib-resistant cells with T790M via inhibition of AKT and ERK signaling and promotion of apoptosis. Furthermore, gefitinib-resistant cells showed enhanced intratumor heterogeneity accompanied by genomic instability and activation of alternative resistance mechanisms compared with dacomitinib-resistant cells; this suggests that the maintenance of EGFR dependency after acquiring resistance might depend on the type of EGFR-TKI. Our results demonstrate that the progression of tumor heterogeneity via both genetic and non-genetic mechanisms might affect osimertinib sensitivity in tumors with acquired resistance harboring EGFR-T790M mutation. |
| 巻・号 | 11(4) |
| ページ | 944-955 |
| 公開日 | 2022-2-1 |
| DOI | 10.1002/cam4.4504 |
| PMID | 35029047 |
| PMC | PMC8855901 |
| MeSH | Carcinoma, Non-Small-Cell Lung* / drug therapy Carcinoma, Non-Small-Cell Lung* / genetics Carcinoma, Non-Small-Cell Lung* / pathology Drug Resistance, Neoplasm / genetics ErbB Receptors Gefitinib / pharmacology Humans Lung Neoplasms* / drug therapy Lung Neoplasms* / genetics Lung Neoplasms* / pathology Mutation Protein Kinase Inhibitors / pharmacology Protein Kinase Inhibitors / therapeutic use |
| IF | 3.491 |
| リソース情報 | |
| ヒト・動物細胞 | PC-9(RCB4455) |