ESTRO 2024 - Abstract Book

S5429

Radiobiology - Tumour biology

ESTRO 2024

Taken together, our data suggests that TRIB1 may modulate p53 function through COP1 mediated degradation and/or HDAC1 possibly via deacetylation. Therefore, targeting TRIB1 could spare p53 function in these cells thereby promoting treatment sensitization to RT/TMZ.

Keywords: Glioblastoma, TRIB1, p53

References:

Signal Transduction and Targeted Therapy (2017) 2, e17040; doi:10.1038/sigtrans.2017.40

Singh, K., Han, C., Fleming, J.L. et al. TRIB1 confers therapeutic resistance in GBM cells by activating the ERK and Akt pathways. Sci Rep 13, 12424 (2023)

Mol Neurobiol (2017) 54:5008–5016

2788

Digital Poster

Characterization of radiosensitization by kinase inhibition in preclinical pancreatic cancer models

Julia Pangerl 1 , Lukas Spieß 1 , Patricia Hoffmüller 1 , Alessia Crocione 1 , Christopher Kessler 1 , Svenja Wiechmann 2,3 , Günter Schneider 4,5 , Roland M. Schmid 4 , Bernhard Kuster 2,3,6 , Daniela Schilling 1,7 , Stephanie E. Combs 1,2,7 , Sophie Dobiasch 1,2,7 1 Technical University of Munich (TUM), Department of Radiation Oncology, Munich, Germany. 2 German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany. 3 Technical University of Munich (TUM), Chair of Proteomics and Bioanalytics, Freising, Germany. 4 Technical University of Munich (TUM), Medical clinic and polyclinic II, Munich, Germany. 5 University Medical Center Göttingen, Department of General, Visceral and Pediatric Surgery, Göttingen, Germany. 6 Technical University of Munich (TUM), Bavarian Center for Biomolecular Mass Spectrometry, Freising, Germany. 7 Helmholtz Munich, Institute of Radiation Medicine (IRM), Neuherberg, Germany

Purpose/Objective:

Pancreatic ductal adenocarcinoma (PDAC) has an overall 5-year survival rate of less than 10% [1]. Only 20% of patients have a surgically resectable disease, which is the only curative option. Neoadjuvant radiotherapy (RT) after induction chemotherapy might be used for tumor downsizing, aiming for a secondary resection [2]. Due to high genetic diversity and heterogeneous radiosensitivity of tumors RT fails in about 70% of all cases [3]. Our previous research project identified a network of signaling pathways using phosphoproteomics and demonstrated a radiosensitization by the kinase inhibitors Rabusertib (targeting checkpoint kinase 1, CHEK1i) and Defactinib (targeting focal adhesion kinase, FAKi) in radioresistant murine PDAC cells [4].