Synergistic Potential of GLP-1 Receptor Agonists and Radiotherapy in Breast Cancer Treatment: A New Therapeutic Avenue (TROD-GROG 006).

Abstract

Introduction: GLP-1 receptor agonists (GLP-1 RAs) are anti-diabetic agents known for their anti-inflammatory and antioxidant properties. This study investigates the synergistic effects of GLP-1 RAs and radiotherapy (RT) on breast cancer in a preclinical mouse model.

Materials and methods: Female BALB/c mice were inoculated with 4T1 breast cancer cells and divided into five groups: control, placebo, GLP-1 RA alone, RT alone, and combination treatment. GLP-1 RA was administered intraperitoneally, and a single 8 Gy RT dose was applied. Tumor volumes, histopathological changes, cytokine expression, and apoptosis-related protein profiles were evaluated. In vitro, 4T1 cell viability was assessed following GLP-1 RA and/or RT exposure.

Results: Combination therapy significantly reduced tumor volume compared to RT or GLP-1 RA alone. Histological analysis revealed improved tissue morphology with the combined approach. Immunohistochemical staining showed decreased expression of pro-inflammatory markers (IL-6, TNF-α) and angiogenic factors (VEGF-A, FGF-2), while pro-apoptotic proteins (caspase-3, BAD, p53) were elevated. In vitro findings confirmed a synergistic reduction in cell viability with combined treatment.

Discussion: The results indicate that GLP-1 RAs potentiate the antitumor effect of RT in breast cancer, primarily through modulation of apoptosis and the tumor microenvironment.

Conclusion: GLP-1 RAs may be effective adjuvants to RT in breast cancer, particularly for patients with diabetes. The dual benefit of tumor sensitization and protection of normal tissues offers a promising therapeutic avenue.