The developmemt for prevention of breast cancer for BRCA carriers

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21457
• Project/Area Number (Other): 18H06376 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0908:Society medicine, nursing, and related fields
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Ono Hisako 京都府立医科大学, 医学(系)研究科(研究院), 助教 (50827326)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: BRCA / 遺伝性乳がん卵巣がん症候群 / クルクミン / ケミカルバイオロジー / BRCAness / PARP阻害薬 / オラパリブ

Outline of Final Research Achievements

Based on the result that curcumin, one of natural compounds with anti-tumor effects induces BRCAness, we used it as a chemical probe and searched for a molecular biomarker which may be useful for prevention and therapies of hereditary breast and ovarian cancers.
We generated curcumin-fixed magnetic FG beads through chemical biology approaches, and identified the curcumin-binding proteins. Among these identified proteins, molecule W was a candidate. Knockdown of W downregulated the BRCA1 and BRCA2 expression at the mRNA levels, as well as the treatment by clinically used inhibitory drugs of W. These findings suggest that molecule W has the possibility of a key molecule to induce BRCAness.

Free Research Field

乳癌　遺伝性腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究によりクルクミンの結合タンパク質のひとつである分子WがBRCAness誘導に関連している可能性が示唆された。現在、PARP阻害剤が遺伝性乳癌や卵巣癌の治療で臨床応用されている。PARP阻害剤の効果はBRCAnessの状態であれば感受性が増強することが想定されるため、今後、分子Wに関するさらなる解析を進めることで遺伝性乳がん卵巣がん症候群の予防や治療に役立つ可能性がある。