Drug Interactions and Biological Effects via Amino Acid Transporters in Neutron Capture Therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16698
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Osaka Medical and Pharmaceutical University
• Principal Investigator: Hiroyuki Shiba 大阪医科薬科大学, 医学部, 非常勤医師 (60910693)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 悪性脳腫瘍 / ホウ素中性子捕捉療法 / アミノ酸トランスポーター / 薬物相互作用 / ドラッグリポジショニング / 抗てんかん薬

Outline of Final Research Achievements

Malignant meningioma (MM) is a rare brain tumor with high risk of recurrence. The treatment of that is difficult and has been discouraging. We have shown that boron neutron capture therapy (BNCT) may be a promising treatment option for this tumor. The efficacy of BNCT relies on boron compounds. We are not satisfied with the efficacy of BNCT today. Because producing new boron compounds are very complicated and cost much, we decided to use conventional boron compounds and existing drugs. We discovered that combined use of boronophenylalanine (BPA) and lamotrigine (LTG; one of antiepileptic drugs) made MM cell lines increase boron uptake. BPA is localized to tumor cells by L-type Amino Acid Transporter 1 (LAT1). It has been already shown that LTG upregulate the expression of LAT1. LTG can improve the efficacy of BNCT by promoting the expression of LAT1. In the future, we have to find the way to visualize LAT1 expression, which make us predict therapeutic effects of BNCT for patients.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

ホウ素中性子捕捉療法(BNCT)は、これまで治療困難とされてきた悪性脳腫瘍に対する新たな治療の選択肢として注目されている。ただ、BNCTの治療効果は、使用するホウ素化合物によって左右され、現在使用されているboronophenylalanine(BPA)では、まだ十分な効果とは言えない。過去に各国で様々な新規ホウ素化合物が考案されてきたが、実用化には至っていない。我々は既存の医薬品とBPAを併用するという費用対効果に優れた新たな手法を考案し、今回の研究でその実現可能性を見出した。臨床での応用にはまだ時間を要するが、この本邦独自の手法によって、BNCTの治療効果の更なる向上が期待される。