ESTRO 2024 - Abstract Book

S5283

Radiobiology - Normal tissue radiobiology

ESTRO 2024

Conclusion:

The experimental model captured acute and late RT-induced normal brain toxicity, at both the cellular and functional (behavioural) levels. Combination treatment with RT and AZD1390 showed no evidence of exacerbating RT-induced effects on neural stem and precursor cells. In contrast, this combination therapy caused a marked reduction in potentially pro-inflammatory microglia/macrophage cell numbers. Crucially, early evidence that the combination of RT and AZD1390 protects against late RT-induced cognitive decline was obtained in behavioural studies.

Taken together with its potent radiosensitization of GBM cells [3], these findings support ongoing investigation of AZD1390 and RT as a promising therapeutic strategy in patients with GBM.

Keywords: Brain, late-effects, ATM

References:

1. Zhao Y, Simon M, Seluanov A, Gorbunova V. DNA damage and repair in age-related inflammation. Nat Rev Immunol. 2023;23(2):75-89. doi:10.1038/s41577-022-00751-y 2. Lumniczky K, Szatmári T, Sáfrány G. Ionizing Radiation-Induced Immune and Inflammatory Reactions in the Brain. Front Immunol. 2017;8:517. Published 2017 May 5. doi:10.3389/fimmu.2017.00517 3. Durant ST, Zheng L, Wang Y, Chen K, Zhang L, Zhang T, Yang Z, Riches L, Trinidad AG, Fok JHL, Hunt T, Pike KG, Wilson J, Smith A, Colclough N, Reddy VP, Sykes A, Janefeldt A, Johnström P, Varnäs K, Takano A, Ling S, Orme J, Stott J, Roberts C, Barrett I, Jones G, Roudier M, Pierce A, Allen J, Kahn J, Sule A, Karlin J, Cronin A, Chapman M, Valerie K, Illingworth R, Pass M. The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models. Sci Adv. 2018 Jun 20;4(6):eaat1719. doi: 10.1126/sciadv.aat1719. PMID: 29938225; PMCID: PMC6010333.