S2643
Radiobiology - Tumour radiobiology
ESTRO 2026
Figure 1 A, B & CIn contrast, a non-linear dose- response was seen for transcriptomic changes, with an early defensive phase characterised by upregulation of NF- κ B signalling and immune activation at 10-20Gy (Figure 2A), followed by downregulated growth factor signalling (particularly TGFß) at 20-30Gy (Figure 2B). Regardless, there was consistent upregulation of genes involved in dopaminergic signalling at all dose levels. The expression of polymerase theta also significantly increased when compared with treatment-naïve PDOs (Figure 2C). Dose-dependent changes in tumour methylation were observed but did not clearly correlate with gene expression patterns. Figure 2 A, B & C Conclusion: Treatment of PDOs with clinically-relevant high-dose fractionated radiotherapy schedules enable the analysis of tumour evolution and plasticity in response to radiotherapy. In OAC, this approach identifies polymerase theta and dopamine signalling as potential novel targets for radiosensitisation. References: 1 Hoeppner J, Brunner T, Schmoor C et al. Perioperative chemotherapy or preoperative chemoradiotherapy in esophageal cancer. N Engl J Med 2025;392:323-335. Keywords: Oesophageal adenocarcinoma; Evolution
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