AACR 2023 Poster 2822

Maximizing Radiotherapy Impact: A Novel Pre-clinical Platform for Screening of Radiosensitizing Agents in Patient-derived Tumor Organoids

Liza Wijler, Jara Garcia, Muntaser Abdulrahman, Linda van Seters, My Nguyen, Annelot Staes, Bram Herpers, Leo Price, Marrit Putker

Radiotherapy (RT) is widely used for various cancer types. To optimize effectiveness of current therapeutic regimens, there is a clinical need to enhance radiotherapy mediated killing by radiosensitizing agents. Radiosensitizers show great potential, but preclinical drug efficacy testing methods are limited. Although some radiosensitizing agents have been identified, potential radiosensitizing effects of standard of care (SoC) as well as novel anticancer drugs remain largely unknown. This study presents a unique chemoradiation combination screening platform that enables radiosensitizer discovery by showing in-depth insight in cytostatic-and toxic changes and RT-drug synergy in patient-derived tumor organoids (PDOs).

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• How the incorporation of radiosensitivity testing in both the HCI and CTG-based organoid drug screening platforms can be used to determine RTsensitive:insensitive profiles across different cancer indications and genetic backgrounds and assess radiosensitizing potential of SOCs and novel therapeutics. 
  
  
• A novel platform for testing potential radiosensitizing anti-cancer agents that holds great promise for advancing drug discovery in a clinically relevant and readily available PDO panel, harboring a wide range of RT-sensitive to insensitive models.
  
  
• How CTG and HCI read-outs offer both fast and in-depth assessment of cytotoxic and cytostatic effects and organoid morphology, creating omnipotent potential for tailored compound screening of radiosensitizers.

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