Overcoming Molecular Targeted Drug Resistance in Aromatase Inhibitor-Resistant Breast Cancer.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09084
• 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: Fujita Health University
• Principal Investigator: Hikichi Masahiro 藤田医科大学, 医学部, 研究員 (80794130)
• Co-Investigator(Kenkyū-buntansha): 林 孝典 藤田医科大学, 医学部, 講師 (40724315) ; 下野 洋平 藤田医科大学, 医学部, 教授 (90594630) ; 喜島 祐子 藤田医科大学, 医学部, 教授 (60381175) ; 内海 俊明 藤田医科大学, 医学部, 教授 (10176711)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 難治性乳がん治療 / 乳がん / パルボシクリブ

Outline of Final Research Achievements

A cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib (Palb) emerged as an effective treatment option for aromatase inhibitor-resistant breast cancers. However, molecular mechanisms and predictive biomarkers for Palb-resistance are not elucidated. This study established the 30 lines of long-term estrogen-deprived (LTED) MCF7 breast cancer cells as a model for aromatase inhibitor-resistant breast cancers. We explored factors involved in the aromatase inhibitor-resistance in breast cancers.
The results revealed that the higher the expression of Rab31, the more effective Palb was. This study suggests that Rab31 is a biomarker for Palb resistance in aromatase inhibitor-resistant breast cancer and a negative regulator.

Free Research Field

乳がん

Academic Significance and Societal Importance of the Research Achievements

本研究によって明らかになった，Rabをバイオマーカーとして利用することによりPalbの適正な利用が可能になる。また，Rab31とPalbの分子メカニズムを明らかにすることで，難治性乳がんの新たな治療法開発に発展させられる可能性がある。