Abstract
Abstract Inhibitors of PARP sensitize cancers to radiation through mechanisms involving DNA damage, replication stress, and PARP trapping. These mechanisms may also activate innate immune signaling leading to Type I Interferon (T1IFN) production. The overall goal of this talk is to explore the hypothesis that PARP inhibitors potentiate radiation-induced T1IFN to activate an anti-tumoral immune response in pancreatic cancer (PDAC) and H3K27 altered-diffuse midline glioma (DMG). Preclinical data supporting this hypothesis will be described including the effects PARP1/2 inhibition (olaparib) as well as PARP1 selective inhibition (AZD5305, AZD4974) in combination with radiation on T1IFN production, modulation of the tumor microenvironment, and the contributions of CD8+ T and NK cells to anti-tumor immune responses in PDAC and DMG, respectively. Furthermore, the translation of these preclinical studies to early phase clinical trials will be discussed. Citation Format: Meredith M. Morgan. Enhancing radiation-induced anti-tumoral immune responses with PARP inhibitors in PDAC and DIPG. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA12
Published Version
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