ESTRO 2025 - Abstract Book

S3977

Radiobiology - Tumour radiobiology

ESTRO 2025

1482

Mini-Oral Synergistic Potential of GLP-1 Receptor Agonists and Radiotherapy in Breast Cancer Treatment: A New Therapeutic Avenue: TROD-GROG 006 Özüm Atasoy 1 , Elvan Anadol 2 , Atiye S Yar Saglam 3 , Eyüb Y Akdemir 4 , Yasemin Şengün 5 , Ece Atak 6 , Şefika Dinçer 7 , Duygu D Usta Salimi 3 , Aslı Emniyet Sert 8 , Gülnur Take Kaplanoğlu 8 , Yıldız Güney 9 1 Radiation Oncology, Giresun Research and Training Hospital, Giresun, Turkey. 2 Laboratory Animal Breeding and Experimental Researches Center, Gazi University, Ankara, Turkey. 3 Medical Biology and Genetics, Gazi University, Ankara, Turkey. 4 Radiation Oncology, Miami Cancer Institute, Miami, USA. 5 Radiation Oncology, Van Research and Training Hospital, Van, Turkey. 6 Radiation Oncology, Akdeniz University, Antalya, Turkey. 7 Radiation Oncology, Van Yüzüncü Yıl University, Van, Turkey. 8 Histology and Embryology, Gazi University, Ankara, Turkey. 9 Radiation Oncology, Etlik City Hospital, Ankara, Turkey Purpose/Objective: GLP-1 receptor agonists (GLP-1 RAs) are primarily used in diabetes treatment for enhancing insulin sensitivity and secretion. Emerging evidence highlights their potential anti-cancer effects, including anti-inflammatory and antioxidant properties. This study explores the combined impact of GLP-1 RAs and radiotherapy (RT) on breast cancer in a Balb/c mouse model, focusing on tumor progression, histopathology, and protein markers of inflammation, apoptosis, and extracellular matrix remodeling. Material/Methods: Fifty-five female Balb/c mice were injected with 4T1 triple-negative breast cancer cells. The mice were divided into five groups: control, placebo, GLP-1 RA, RT, and combined GLP-1 RA with RT. GLP-1 RA (exenatide) was administered intraperitoneally for seven days, and RT (8 Gy) was applied on the fourth day. Tumor size and body weight were monitored throughout. Tumor tissues were analyzed histologically and immunohistochemically for VEGF-A, FGF-2, collagen-1, IL-6, TNF-α, and TGF-β expression. Apoptotic markers and cell viability were assessed through MTT assays. Results: The combination of GLP-1 RA and RT significantly reduced tumor size compared to other groups (p<0.05). Histological analysis revealed restored healthy tissue architecture, with decreased necrotic areas and improved epithelial organization. Immunohistochemistry showed a significant reduction in VEGF-A, FGF-2, and collagen-1 expression in the combined treatment group, indicating reduced angiogenesis and tumor stiffness. Additionally, IL-6 and TNF-α levels were reduced, suggesting decreased inflammation, while TGF-β expression was moderated, reflecting lower extracellular matrix remodeling (Figure 1). Apoptotic markers such as caspase-3 and caspase-7 were significantly elevated, confirming enhanced cancer cell death (Figure 2). In vitro assays showed a significant decrease in 4T1 cell viability after combined treatment (p<0.01).