Development of novel therapy for triple negative breast cancer by regulation of HMG-CoA reductase

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09081
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kyorin University
• Principal Investigator: ASAGA SOTA 杏林大学, 医学部, 講師 (00327529)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 乳癌 / トリプルネガティブ / HMG-CoA レダクターゼ / 薬剤耐性 / 新規治療開発

Outline of Final Research Achievements

We investigated the association between HMG-CoA reductase (HMGCR) expression levels in breast cancer tissue and the prognosis of the case by immunohistostaining with specific antibodies to HMGCR. As a result, weak to strong expression of HMGCR was observed in all cases, but no significant relationship was found between the expression intensity and the prognosis.
Next, we clarified that drug resistance was acquired in the triple negative breast cancer (TNBC) cell line (MDA-MB468) co-cultured with activated macrophages in experiments using a co-culture system. In addition, the expression level of HMGCR in this TNBC cell line co-cultured with activated macrophages was significantly higher than that in the cell line co-cultured with non-activated macrophages, suggesting that HMGCR is involved in drug resistance.

Free Research Field

乳腺腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究は予後不良かつ難治性とされる、ホルモン感受性陰性かつHER2陰性のいわゆる「トリプルネガティブ」乳癌(TNBC)に対する新規治療開発を目指した研究である。本研究ではTNBCの組織においてHMGCRの発現が認められることを明らかにし、加えて、TNBC細胞株における薬剤耐性にHMGCRが関与する可能性について指摘した。本研究の成果は、今後のTNBCに対する新規治療開発の重要な一歩であり、将来的に多くのTNBC患者の予後改善につながることが期待される。