ESTRO 2024 - Abstract Book

S5334

Radiobiology - Tumour biology

ESTRO 2024

Primary GBM cells with wild-type p53 and knockdown of PSMA7 had reduced cell viability in vitro after treatment with a small molecule MDM2 inhibitor compared to control cells. Furthermore, we observed that RT enhanced cell death in GBM cells in vitro when combined with inhibition of PSMA7 and MDM2. We also determined the expression of apoptotic proteins in GBM cells in response to individual and combination treatments of PSMA7 knockdown, MDM2 inhibition, and/or RT. In addition, PSMA7 knockdown was found to inhibit the proteolytic activities of GBM cells, indicating a potential mechanism by which decreased degradation of wild-type p53 may enhance sensitivity of GBM cells to MDM2 inhibition and RT.

Conclusion:

Our study demonstrated that silencing PSMA7 in combination with RT and MDM2 inhibition increases cell death in patient-derived primary GBM cells with wild-type p53 status in vitro. Consequently, targeting PSMA7, such as by using blood-brain barrier permeable small molecule inhibitors, combined with MDM2 inhibition and the current standard of care for GBM (i.e., maximal surgical resection, radiotherapy, and concomitant and adjuvant temozolomide) holds potential for improving outcomes of GBM patients with wild-type p53.

Keywords: PSMA7, GBM, p53

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Digital Poster

Characterization of radiation response of pancreatic tumor cells in correlation with MYC expression

Patricia Hoffmüller 1 , Julia Pangerl 1 , Alessia Crocione 1 , Günter Schneider 2,3 , Roland M Schmid 2 , Daniela Schilling 1,4 , Stephanie E Combs 1,4,5 , Sophie Dobiasch 1,4,5 1 Technical University of Munich (TUM), Department of Radiation Oncology, Munich, Germany. 2 Technical University of Munich (TUM), Medical clinic and polyclinic II, Munich, Germany. 3 University Medical Center Göttingen, Department of General, Visceral and Pediatric Surgery, Göttingen, Germany. 4 Helmholtz Zentrum München, Institute of Radiation Medicine (IRM), Neuherberg, Germany. 5 Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Munich, Germany

Purpose/Objective:

Treating pancreatic ductal adenocarcinoma (PDAC) patients remains challenging since extensive genetic heterogeneity and a variation of intrinsic radiosensitivity often characterize the tumors. One treatment option for patients with locally advanced PDAC consists of neoadjuvant radiotherapy after induction chemotherapy and consequent surgery.

Our previous research showed a correlation between high MYC expression and tumor radioresistance in murine PDAC cell lines by Gene Set Enrichment Analysis of RNA sequencing data and radioresponse data.