Development of a novel biomarker predicting response to HER2 inhibitor

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07778
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Prefectural University of Hiroshima
• Principal Investigator: NAGAO NORIO 県立広島大学, 生物資源科学部, 准教授 (40227989)
• Co-Investigator(Kenkyū-buntansha): 片山 博志 岡山大学, 医歯薬学総合研究科, 准教授 (90713975) ; 笹井 香織 岡山大学, 医歯薬学総合研究科, 助教 (50722162)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: HER2陽性乳癌 / eEF1A2 / 予測バイオマーカー / アポトーシス

Outline of Final Research Achievements

We studed the effectiveness of expression analysis of the translation factor eEF1A2 as a companion diagnostic for predicting HER2-positive breast cancer.On IHC analysis, eEF1A2 expression decreased with tumor stage progression in HER2-positive breast cancer cases, and the prognosis was better for patients with higher eEF1A2 expression.In signal pathway analysis of HER2-positive breast cancer, we found that eEF1A2 functions as a cancer-suppressing protein by forming a protein complex with PTEN. And we found that in eEF1A2 overexpressing HER2-positive breast tumor cell lines, phosphorylation levels of Bcl-2 family proteins decreased and cleaved caspase 3 expression increased. We suggest that eEF1A2 is the excellent predictive biomarker with a role in enhancing apoptotic activity in HER2-positive breast tumor cells.

Free Research Field

細胞工学

Academic Significance and Societal Importance of the Research Achievements

HER2分子標的薬の効果を予測できる新規コンパニオン診断薬の開発は、非適用患者の治療回避と早急な治療方針策定のためにも重要かつ喫緊な課題である。HER2分子標的薬感受性決定におけるeEF1A2の重要性を踏まえ、eEF1A2発現検査をHER2分子標的薬治療の新たなコンパニン診断薬として利用することを提唱し、その分子基盤の明確化と有効性の確立を目指し、eEF1A2がHER2陽性乳癌細胞においてアポトーシス活性を高める役割を持つ優れた予測バイオマーカーであることを示唆した。今後さらに解析を進めることで、eEF1A2遺伝子発現解析がHER2阻害剤治療の予後予測し得る有用バイオマーカーとして確立したい。