Development of minimally invasive diagnostic methods and epigenomic therapies focusing on founder epi-drivers in lung adenocarcinoma.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02894
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: Imoto Issei 愛知県がんセンター(研究所), 研究所長, 研究所長 (30258610)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肺腺癌 / エピゲノム / ドライバー / リキッドバイオプシー / 治療標的

Outline of Final Research Achievements

Although various driver mutations have been identified and molecular targeted therapies are being developed in lung adenocarcinoma (LAD), many cases lack these driver mutations and drug-resistance is easily acquired based on the temporal and spatial heterogeneity of cancers. In this study, we focused on the founder epi-driver type tumor suppressor genes (TSGs), which shows frequent tumor-specific hypermethylation from early stage, as a diagnostic and therapeutic target molecule that can overcome these issues. As a result, we have developed epi-markers that can be detected in plasma to detect early stage LAC or recurrence and predict therapeutic efficacy. We also identified therapeutic target epi-driver TSGs and related molecular pathways, and selected chemical compounds that mimic the activation of these pathways by through in silico screening.

Free Research Field

ゲノム医科学

Academic Significance and Societal Importance of the Research Achievements

がん領域では、遺伝子パネル検査やエクソーム、全ゲノム解析の結果から、腫瘍の網羅的な解析による癌細胞特異的治療標的検出や血漿を使った早期、再発、治療効果診断に有用な遺伝子変異の同定が進んでいる。特にリキッドバイオプシーは低侵襲で繰り返し行える検査法として臨床実装されており、腫瘍組織のゲノム情報が不要な各癌種に固有のバイオマーカーの同定は、早期のスクリーニング検査や組織のない症例での治療効果の評価、原発不明がんの原発巣予測などに応用可能な重要課題である。本課題の成果は、肺腺癌の早期診断マーカーとその検出法の開発に有用な情報を提供するもので、臨床応用が見込める点で意義がある。