Formation of a non-clinical research base for treatment aimed to eradicate lung cancer by targeted drugs

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03665
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Kanazawa University
• Principal Investigator: Yano Seiji 金沢大学, がん進展制御研究所, 教授 (30294672)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 分子標的薬 / 抵抗性 / EGFR変異 / ALK融合遺伝子 / NTRK1融合遺伝子

Outline of Final Research Achievements

Cancer cells exposed to targeted drugs emerge tolerant cells that allow some to survive as resistant cells and later proliferate. In this study, we found that EGFR-mutated lung cancer cells with low AXL expression emerge tolerant cells to the EGFR inhibitor osimertinib by increasing the expression of the transcription factor FOXA1 to activate IGF-1R. We further found that TP53 mutation and STAT3 activation induce apoptosis resistance to ALK inhibitors and cause ALK inhibitor tolerance in ALK rearranged lung cancer cells. In addition, combined use of proteasome inhibitors or STAT3 inhibitors could augment the efficacy of ALK inhibitors against ALK rearranged lung cancer cells.

Free Research Field

臨床腫瘍学

Academic Significance and Societal Importance of the Research Achievements

分子標的薬は標的を有するがん患者に著効するが、一部のがん細胞が抵抗性となって生き残り、再発する原因となる。本研究では一部のがん細胞が生き残るメカニズムとして正常細胞がもともと持っている蛋白質を活性化させたり、がん細胞が持っている遺伝子異常により細胞を死ににくくさせることを明らかにした。この研究成果が分子標的薬の治療効果を高める治療法開発に結び付くことが期待される。