# Evaluation of a Boron-Conjugated SRC Inhibitor Combined with Proton and X-Ray Irradiation in U-87 MG and U-87 MG IDH1R132H Glioma Cell Lines

## TL;DR

This study explores a new boron-based drug combined with proton and X-ray radiation to treat glioma cells, finding early DNA damage effects in IDH1-mutant cells.

## Contribution

The study introduces a novel boron-conjugated SRC inhibitor and evaluates its interaction with proton and X-ray irradiation in glioma cells.

## Key findings

- No significant synergistic effects were observed in cell survival endpoints.
- IDH1-mutant glioma cells showed enhanced acute DNA damage after combined proton irradiation and treatment.
- The results suggest potential for boron-based targeted strategies in specific glioma subtypes.

## Abstract

Background: Adult diffuse gliomas represent one of the most aggressive types of brain tumors. Proton therapy offers a minimally invasive treatment option whose biological effectiveness may be enhanced through nuclear reactions involving boron atoms, leading to the emission of high-LET α-particles. In this study, we investigated the potential enhancement of radiation-induced damage of a novel boron-conjugated, ATP-competitive SRC kinase inhibitor, in the U-87 MG glioma cell line and its isogenic cell line stably expressing the IDH1 R132H mutation. Methods: Glioma cells were exposed to either proton or X-ray irradiation to assess whether any enhancement associated with this boron-delivery strategy was specific to proton interactions. Cell survival assays and analyses of DNA damage responses were conducted in both cell lines. Results: While no significant synergistic effects were observed in survival endpoints, differences emerged at the level of early DNA damage effects, with IDH1-mutant glioma cells displaying an enhanced acute response following combined treatment with proton irradiation. Conclusions: These findings support further pharmacological development of boron-based SRC-targeted strategies and underscore the importance of tailoring therapeutic approaches to specific glioma molecular subtypes.