2017 Fiscal Year Final Research Report
EGFR mutant lung cancer and second generation tyrosine kinase inhibitor: acquired resistance and personalized medicine
| Project/Area Number |
16K19989
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory surgery
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| Research Institution | Kindai University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | 肺癌 / EGFR / チロシンキナーゼ阻害剤 / アファチニブ / ダコミチニブ / L792F / 薬剤耐性 |
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| Outline of Final Research Achievements |
Targeted therapy with tyrosine kinase inhibitors (TKIs) is a standard treatment for patients with epidermal growth factor receptor (EGFR) mutant lung cancer. However, not all EGFR mutations are sensitive to conventional EGFR-TKIs. Additionally, lung cancers inevitably acquire resistance to these TKIs despite the marked initial response.
We found that lung cancers harboring exon 18 mutations were not sensitive to conventional first generation EGFR-TKIs but are sensitive to second generation TKI afatinib. Next, a novel EGFR L792F secondary mutation, in addition to T790M and C797S, was discovered in afatinib-resistant cells. L792F appeared to exhibit sensitivity to other second generation TKI dacomitinib. Dacomitinib induced T790M or C797S secondary mutations as mechanisms of acquired resistance and these mutations were sensitive to currently available TKIs.
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| Free Research Field |
呼吸器外科
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