ESTRO 2025 - Abstract Book

S3975

Radiobiology - Tumour radiobiology

ESTRO 2025

[3] L. M. Madanat-Harjuoja et al. , “Circulating Tumor DNA Is Associated with Response and Survival in Patients with Advanced Leiomyosarcoma”, doi: 10.1158/1078-0432.CCR-21-3951.

1352

Digital Poster Targeted breast cancer radiosensitization using polymeric aptamers Mike Terpstra 1 , Frank Nelissen 2 , Wenny Peeters 1 , Paul Span 1 1 Radiation Oncology, Radboudumc, Nijmegen, Netherlands. 2 Institute for Molecules and Materials, Radboud University, Nijmegen, Netherlands Purpose/Objective: Aptamers are short single-stranded DNA or RNA oligonucleotides that are selected for binding specific targets of interest, such a small molecules, proteins, or cells. A breast cancer specific aptamer has been developed that is able to internalize into cancer cells, but not into normal breast cells [1]. To deliver compounds specifically to cancer cells, we attached this aptamer to a polymer to which further functionalities can be added. This work describes the development of a polymeric aptamer platform targeting homologous recombination using RAD51 siRNAs or - aptamers for breast cancer specific radiosensitization. Material/Methods: Two different RAD51 inhibiting agents were analyzed, a RAD51 siRNA for gene silencing and a RAD51 aptamer selected to bind RAD51 causing the RAD51 single-strand DNA structure to disassemble. RAD51 siRNAs and aptamers were incorporated into a polymeric aptamer platform and their ability to internalize into SKBR3 and HCC1954 both in 2D monolayers and 3D spheroids was visualized. Finally, the radiosensitizing ability of RAD51 siRNA- and RAD51 aptamer- and siRNA-decorated polymeric aptamers was assessed on SKBR3 and HCC1954 cells using RAD51 and 53BP1 foci quantification after irradiation. Results: RAD51 siRNA and/or -aptamers were capable of significantly decreasing DNA damage after irradiation in SKBR3 and HCC1953 breast cancer cells (for specifics and p-values, see figures 1 and 2). A polymer containing a breast cancer targeting aptamer and RAD51 siRNA readily internalized within 24 hrs. Furthermore, treatment with the polymeric RAD51-siRNA aptamer 48 hrs pre-irradiation reduced RAD51 and/or 53BP1 foci containing SKBR3 and HCC1953 cells early (5hrs) and late (24hrs) post-irradiation to levels comparable to siRNA treatment.