Analysis of pemetrexed-resistant mechanism in EGFR mutation positive non-small cell lung cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26830118
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Kawasaki Medical School
• Principal Investigator: Ochi Nobuaki 川崎医科大学, 医学部, 講師 (80611615)
• Co-Investigator(Renkei-kenkyūsha): TAKIGAWA Nagio 川崎医科大学, 総合内科学4, 教授 (60325107)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 非小細胞肺癌 / pemetrexed / EGFR-TKI / 耐性

Outline of Final Research Achievements

Pemetrexed is a key drug in the treatment for the patients with activating EGFR mutation-positive non-small cell lung cancer (NSCLC). However, the relationship between TS up-regulation and EGFR mutation status and the difference of resistant mechanisms among a variety of EGFR mutations remain unclear. We previously reported that TS and dihydrofolate reductase were involved in developing PEM resistance in PC-9 (EGFR exon19 in-frame deletion mutation) and A549 (wild-type EGFR) cells. In this study, TS is significantly up-regulated in H1975 (L858R+T790M mutation) cells. Moreover, epithelial-mesenchymal transition might be an alternative resistant mechanism in H1975 cell. Meanwhile, the sensitivity to EGFR-tyrosine kinase inhibitor was increased in EGFR-mutation positive-PEM resistant cells. These results warrant further preclinical studies and the optimal treatment sequence in EGFR mutation-positive NSCLC patients will be projected.

Free Research Field

呼吸器内科学