Development of BRD4 inhibitor combination therapy for suppressing cardiotoxicity of anticancer drugs

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15676
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: The University of Tokyo
• Principal Investigator: Tochinai Ryota 東京大学, 大学院農学生命科学研究科(農学部), 助教 (90833997)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 抗がん剤 / 心毒性 / BRD4 / microtubule / JQ1 / combretastatin A4

Outline of Final Research Achievements

It is known that a good antitumor effect can be obtained by inhibiting BRD4, which is an important BET family protein in cancer growth. Furthermore, it has become clear that BRD4 inhibitors also have an inhibitory effect on heart failure. Based on these findings, it is expected that chemotherapy with a reduced risk of cardiotoxicity will be possible by using an existing anticancer drug with cardiotoxicity in combination with a BRD4 inhibitor.
Based on the results of non-clinical studies using mice and rats conducted in this study, the risk of cardiotoxicity of combretastatin A4,a microtubule polymerization inhibitors, was reduced by the combined use of a BRD4 inhibitor, and the possibility of developing a new cancer chemotherapeutic method was shown.

Free Research Field

病態生理学、毒性学、循環器学、獣医学、薬理学

Academic Significance and Societal Importance of the Research Achievements

BRD4阻害薬の抗腫瘍効果については多くの期待が集まっており、多くの研究開発が進められている。一方、BRD4阻害薬の抗がん剤誘発性の心筋障害に対する有用性については国内外を含めてほとんど報告がなされていなかった。本研究成果により、BRD4阻害薬の心毒性抑制効果が明らかになり、BRD4阻害薬の応用可能性が広がることで新規がん化学療法の開発に繋がるものと期待される。