Abstract 1836: Radiation effects in normal oral tissues caused by boron neutron capture therapy

Abstract As a promising modality of binary radiation therapy, boron neutron capture therapy (BNCT) combines the advantages of boron-10 delivery agents for tumor-targeting and heavy charged particles for robust cell killing. BNCT has been approved for clinical treatment of head and neck cancer in Japan. However, the heavy ion rays generated from 10B (n, α) 7Li reactions as well as the concurrent gamma ray and thermal neutron radiation during BNCT can not only destroy cancer cells but also inevitably damage normal oral tissues, which constitutes the primary concern for head and neck cancer patients who are suitable for BNCT. Unfortunately, our knowledge about the radiobiology of BNCT-caused oral tissue damage is very limited to date. Therefore, we set out this study to explore the potential mechanisms in oral tissue reactions following BNCT. We collected various oral tissues from a mouse tumor model treated with BNCT and extracted total RNA from tongue tissues of 11 mice (4 controls without BNCT and 7 BNCT-treated samples with 2.5 mM/kg boron-10 delivery agents) for transcriptome sequencing. By comparing the gene expression profiles between the BNCT-treated group and the control group, we identified a total of 308 differentially expressed genes. Notably, these genes were enriched in cell junctions and cell membrane pathways. We further analyzed the interactome network of the 308 genes by common topological algorithms, i.e., Maximal Clique Centrality (MCC), Maximum Neighborhood Component (MNC), and Degree, where we identified a subset of 11 genes based on the shortest paths with the algorithm Stress. Among the 11 genes, both β-Catenin (CTNNB1) and Annexin A2 (ANXA2) were significantly downregulated in BNCT-treated group (P<0.05). Further RT-qPCR analyses confirmed the results, while immunohistochemistry analyses demonstrated consistent BNCT effects in protein levels of these two genes. The encoded protein from CTNNB1 constitutes adherens junctions and anchors the actin cytoskeleton for maintenance of epithelial cell layers. In addition, ANXA2 plays an important role in tissue inflammation and vascular integrity. Thus, we speculate that BNCT induces cell-cell junction disorder through CTNNB1 and ANXA2, leading to damaged cell junctions in blood vessels and normal tissue inflammation. Indeed, disrupted epithelial structure as well as increased interferon-γ expression was detected in oral tissue microenvironment following BNCT. These findings set a basis for developing strategies of normal tissue protection and improving quality of life of head and neck cancer patients that were treated with BNCT. Citation Format: Lin Ma, Yupeng Luo, Jianyue Liu, Yonghui Luo, Zhiyi Wang, Zexi He, Haotian Tang, Qi Liu. Radiation effects in normal oral tissues caused by boron neutron capture therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1836.