ESTRO 2024 - Abstract Book

S5415

Radiobiology - Tumour biology

ESTRO 2024

radiosensitivity with and without inhibitor treatment were analysed using X-irradiation, immunohistochemistry (DNA damage foci) and colony formation assay. A HNSCC tissue micro array (n=300) and Kaplan-Meier analyses were used to analyse patient survival in correlation with molecular biomarkers.

Results:

We identified activated kinases of the Src-family (SFKs) as a tumor specific biomarker in >50% of HNSCC. While the protein expression did not correlate with patient survival, SFK autophosphorylation as a surrogate marker for SFK activity significantly correlated with patients survival, with increased SFK activity being associated with worse prognosis especially for patients who had received radiotherapy. In line with that, activated SFKs were also associated with an increased cellular radioresistance. Vice versa , inhibition of SFK induced radiosensitisation of radioresistant HNSCC cell lines and ex vivo slice cultures of primary HNSCC tissue. This radiosensitization was accompanied by an impaired repair of radiation induced DNA double strand breaks. Moreover, we were also able to show that the inhibitor used is of decisive importance, since more specific inhibitors in particular achieved a better effect than rather non-specific ones.

Conclusion:

Activated SFKs are promising biomarkers and targets for radiosensitization of HNSCC and potentially other entities. Furthermore, our study demonstrates the importance of functional tests especially in the area of kinases which can help to identify future targets beyond gene mutations and expression and with that promote treatment personalization.

Keywords: Kinomics, radiosensitization, HNSCC

2557

Digital Poster

Radiosensitization of glioblastoma by BET (Bromodomain and Extra-Terminal motif) inhibition

Elena Lakotsenina 1 , Sophie Dobiasch 1,2,3 , Stephanie E. Combs 1,2,3 , Daniela Schilling 1,2

1 Department of Radiation Oncology, Technical University of Munich (TUM), Munich, Germany. 2 Institute of Radiation Medicine (IRM), Helmholtz Zentrum München, Neuherberg, Germany. 3 Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Munich, Germany

Purpose/Objective:

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite an aggressive multimodal treatment regimen consisting of surgery, chemo- and radiotherapy, the median overall survival is only 15 months and