L-type amino acid transporter 1 in enhancing boron neutron capture therapy - Mechanisms, challenges and future directions - Review

Q: Why is LAT1 important for boron neutron capture therapy (BNCT)?

LAT1 is frequently upregulated in aggressive tumors and mediates tumor-selective uptake of boron compounds, which is required for effective BNCT.

Q: What transport and mechanistic aspects does the review focus on for LAT1 in BNCT?

The review examines LAT1 structure and function, LAT1-mediated boron transport mechanisms, and regulatory pathways that influence BNCT efficacy.

Q: How can metabolomics methods help clarify LAT1’s role in BNCT?

Advanced metabolomics approaches such as liquid chromatography-mass spectrometry and nuclear magnetic resonance can map metabolic profiles altered by LAT1-mediated boron uptake, supporting understanding of downstream consequences, efficacy, and resistance.

Sep 23, 2026

Uploaded by Mabel

L-type amino acid transporter 1 (LAT1) is a critical molecular target for advancing boron neutron capture therapy (BNCT), which eradicates cancer cells through selective boron accumulation and neutron irradiation. LAT1 is frequently upregulated in aggressive tumors, supporting its role as the key mediator of tumor-selective boron compound uptake. This review analyzes LAT1 structure and function, LAT1-related boron transport mechanisms, and regulatory pathways shaping BNCT efficacy. It also highlights metabolomics strategies using LC-MS and NMR to define LAT1-driven metabolic changes relevant to therapeutic response and resistance, while consolidating challenges and future directions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Contents

1. Introduction

2. Therapeutic principle of BNCT

3. Structure and functional mechanisms of LAT1

4. Mechanistic analysis of LAT1 in BNCT

5. Metabolomic insights into LAT1-mediated metabolism in BNCT

6. Challenges and potential of LAT1 as a therapeutic target in BNCT

7. Future directions

8. Conclusion

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 56: 170, 2025 L‑type amino acid transporter 1 in enhancing boron neutron capture therapy: Mechanisms, challengesand future directions (Review) XIAOQING ZHENG 1 , JIANJI PAN 1 , DONGHAI LIN2 and WEI SHAO 1 1 Precision Medicine Application and Transformation Central Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361000, P.R. China; 2High Field NMR Center, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361000, P.R. China Received April 25, 2025; Accepted August 7, 2025 DOI: 10.3892/ijmm.2025.5611 Abstract. L‑type amino acid transporter 1 (LAT1) has emerged as a critical molecular target for advancing boron neutron capture therapy (BNCT), a promising treatment that leverages selective boron accumulation and neutron irra‑ diation to eradicate cancer cells. The frequent upregulation of LAT1 in aggressive tumors (such as gliomas and specific subtypes of lung and breast cancer) underpins its essential role as the principal mediator of tumor‑selective boron compound uptake in BNCT. The present review comprehensively exam‑ ines the structure and function of LAT1, the mechanistic principles of boron transport (including LAT1 mediation) and the key regulatory pathways governing BNCT efficacy. Building on this and given the role ofLAT1 in reprogramming tumor metabolism through amino acid transport, advanced metabolomics tools, particularly liquid chromatography‑mass spectrometry and nuclear magnetic resonance, offer a novel approach for clarifying the contribution of LAT1 to BNCT. These techniques hold significant potential to map metabolic profiles altered by LAT1‑mediated boron compound uptake, thereby elucidating downstream biochemical consequences relevant to the therapeutic efficacy and resistance mechanisms. Synthesizing the dual role of LAT1 as both a vulnerability and therapeutic target in BNCT, the present review system‑ atizes key challenges, including the need for selective boron Correspondence to: Dr Wei Shao, Precision Medicine Application and Transformation Central Laboratory, Xiamen Humanity Hospital, Fujian Medical University, 3777 Xianyue Road, Xiamen, Fujian 361000, P.R. China E‑mail: [vivishao@foxmail.com](vivishao@foxmail.com) Professor Donghai Lin, High Field NMR Center, College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Xiamen, Fujian 361000, P.R. China E‑mail: [dhlin@xmu.edu.cn](dhlin@xmu.edu.cn) Key words: L‑type amino acid transporter 1, boron neutron capture therapy, aggressive tumors, boron transport, tumor metabolism compounds, resistance mechanisms and off‑target effects, while mapping actionable pathways to unlock its potential via refined regulation strategies, next‑generation delivery agents and personalized approaches. By addressing these knowledge gaps, this synthesis provides a foundational framework to harness LAT1‑targeted BNCT, offering potential to advance precision oncology paradigms and improve clinical outcomes for patients with LAT1‑enriched tumors. Contents 1. Introduction 2. Therapeutic principle of BNCT 3. Structure and functional mechanisms of LAT1 4. Mechanistic analysis of LAT1 in BNCT 5. Metabolomic insights into LAT1‑mediated metabolism in BNCT 6. Challenges and potential ofLAT1 as a therapeutic target in BNCT 7. Future directions 8. Conclusion 1. Introduction Cancer remains a global health burden, with aggressive tumors such as glioblastoma (GBM) presenting some of the most chal‑ lenging scenarios in oncology. Despite the long‑standing use of conventional therapies (such as surgery, radiotherapy and chemotherapy), treatment outcomes remain suboptimal due to therapeutic resistance and tumor recurrence. For patients with GBM, even aggressive multimodal approaches yield a median survival time of <15 months and a 5‑year survival rate <5%(1), underscoring the urgent need for novel strategies that sel

FAQs

Why is LAT1 important for boron neutron capture therapy (BNCT)?

LAT1 is frequently upregulated in aggressive tumors and mediates tumor-selective uptake of boron compounds, which is required for effective BNCT.

What transport and mechanistic aspects does the review focus on for LAT1 in BNCT?

The review examines LAT1 structure and function, LAT1-mediated boron transport mechanisms, and regulatory pathways that influence BNCT efficacy.

How can metabolomics methods help clarify LAT1’s role in BNCT?

Advanced metabolomics approaches such as liquid chromatography-mass spectrometry and nuclear magnetic resonance can map metabolic profiles altered by LAT1-mediated boron uptake, supporting understanding of downstream consequences, efficacy, and resistance.

Sep 23, 2026

Uploaded by Mabel