Molecular Mechanisms of Specific Cellular DNA Damage Response and Repair Induced by the Mixed Radiation Field During Boron Neutron Capture Therapy.

Kamila Maliszewska-Olejniczak,Agnieszka Korgul,Damian Kaniowski,Martyna Araszkiewicz,Katarzyna Tymińska

doi:10.3389/fonc.2021.676575

Abstract

The impact of a mixed neutron-gamma beam on the activation of DNA damage response (DDR) proteins and non-coding RNAs (ncRNAs) is poorly understood. Ionizing radiation is characterized by its biological effectiveness and is related to linear energy transfer (LET). Neutron-gamma mixed beam used in boron neutron capture therapy (BNCT) can induce another type of DNA damage such as clustered DNA or multiple damaged sites, as indicated for high LET particles, such as alpha particles, carbon ions, and protons. We speculate that after exposure to a mixed radiation field, the repair capacity might reduce, leading to unrepaired complex DNA damage for a long period and may promote genome instability and cell death. This review will focus on the poorly studied impact of neutron-gamma mixed beams with an emphasis on DNA damage and molecular mechanisms of repair. In case of BNCT, it is not clear which repair pathway is involved, and recent experimental work will be presented. Further understanding of BNCT-induced DDR mechanisms may lead to improved therapeutic efficiency against different tumors.

Highlights

Boron neutron capture therapy (BNCT) is a radiation therapy that can selectively target neoplastic tissue with an advantage over conventional radiotherapies
We aimed to describe the molecular mechanisms of cellular response to DNA damage, DNA damage response (DDR) induced by boron neutron capture therapy (BNCT) with an emphasis on mixed field radiation, and effects of low and high linear energy transfer (LET) radiation in different cancer cell lines
The results indicate that the dual inhibition of epidermal growth factor receptor (EGFR) and HER2 by afatinib, used for the treatment of non-small cell lung carcinoma (NSCLC), makes cells sensitive to radiation and reduces cell invasiveness

Summary

Introduction

Boron neutron capture therapy (BNCT) is a radiation therapy that can selectively target neoplastic tissue with an advantage over conventional radiotherapies. BNCT is a binary approach in which boron-10 (10B)-labeled compounds such as low molecular weight boron-containing drugs, boronophenylalanine (BPA) or sodium borocaptate (BSH), are administered before irradiation with thermal or epithermal neutrons [1,2,3,4]. This concept assumes that the interaction of thermal neutrons ( [11B*]

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