ESTRO 2024 - Abstract Book

S5393

Radiobiology - Tumour biology

ESTRO 2024

Figure 2: Tumoroids of 3 cell lines showing the radiosensitivity effect of AZD6738 treated with and without radiotherapy (0, 2, 4Gy)

Conclusion:

High replicative stress is induced by CIC::DUX4 oncogenic fusion. This is the first study, to the best of our knowledge, to show the radiosensitisation effect of ATR inhibition in three tumoroid models of CDS. Interestingly, a radiosensitisation effect was also present with non-cytotoxic concentration of ATRi in both monolayer and organoid models. Further investigation is undergoing to determine the efficacy in vivo.

Keywords: CIC-DUX4 sarcoma, ATRi, Replicative stress

References:

(1) Antonescu CR, Owosho AA, Zhang L, Chen S, Deniz K, Huryn JM, Kao YC, Huang SC, Singer S, Tap W, Schaefer IM, Fletcher CD. Sarcomas With CIC-rearrangements Are a Distinct Pathologic Entity With Aggressive Outcome: A Clinicopathologic and Molecular Study of 115 Cases. Am J Surg Pathol. 2017 Jul;41(7):941-949. doi: 10.1097/PAS.0000000000000846. PMID: 28346326; PMCID: PMC5468475. (2) Nickoloff JA, Boss MK, Allen CP, LaRue SM. Translational research in radiation-induced DNA damage signaling and repair. Transl Cancer Res. 2017 Jul;6(Suppl 5):S875-S891. doi: 10.21037/tcr.2017.06.02. PMID: 30574452; PMCID: PMC6298755.

(3) Menolfi, D., Zha, S. ATM, ATR and DNA-PKcs kinases—the lessons from the mouse models: inhibition ≠ deletion. Cell Biosci 10, 8 (2020). https://doi.org/10.1186/s13578-020-0376-x