Establishment of personalized treatment for small cell lung cancer by DNA damage repair capability

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K07197
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Tottori University
• Principal Investigator: MAKINO HARUHIKO 鳥取大学, 医学部, プロジェクト研究員 (20467707)
• Co-Investigator(Kenkyū-buntansha): 木下 直樹 鳥取大学, 医学部附属病院, 助教 (40750336)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 小細胞癌 / DNA-PKcs

Outline of Final Research Achievements

In our study, we found that non-small cell lung cancer cell lines with EGFR mutations, in which EGFR signaling is constantly activated, are more radiosensitive, and that in these cell lines, EGFR translocated into the nucleus binds to DNA-PKcs and influences radiosensitivity. In this study, we found that each small cell lung cancer cell line has different radiosensitivity, and that the expression of nuclear EGFR and DNA-PKcs are different in each cell line. We also found that small cell lung cancer cells are more susceptible to inhibition of cell proliferation and induction of apoptosis in response to DNA-PKcs inhibitors than non-small cell lung cancer cells.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

近年、非小細胞肺癌に対しては分子標的治療による個別化治療が発展しているが、小細胞癌については分子標的治療薬の有効性が確認できず個別化治療は進んでいない。本研究において、小細胞肺癌細胞株毎に放射線照射後の核内EGFRの発現やDNA-PKcsの発現量が異なることやDNA-PKcs阻害薬の治療効果が明らかになった。これらの結果から小細胞肺癌の分子標的治療の開発につながり、小細胞肺癌に対する治療の発展が期待できる。