Akademik Veri Yönetim Sistemi
X. International Congress of Molecular Medicine, İzmir, Türkiye, 23 - 27 Eylül 2024, sa.9, ss.67, (Özet Bildiri)
HER2 overexpression is observed in 20-30% of breast cancers and is associated with a poor prognosis. Trastuzumab, a monoclonal antibody targeting HER2, is a standard therapy for HER2-positive breast cancer. However, resistance develops in approximately 50% of patients within a year, necessitating new therapeutic strategies. The Hedgehog (Hh) signaling pathway, known for maintaining cancer stem cell properties (stemness), may contribute to trastuzumab resistance in HER2-positive breast cancer. This study investigated the role of Hedgehog signaling in sustaining stemness and promoting trastuzumab resistance in HER2-positive breast cancer cell lines. Trastuzumabresistant SKBR3 and HCC1954 cell lines were generated through continuous trastuzumab exposure. Cells were treated with GANT61 (Hh inhibitor, 10 µM) or SAG21K (Hh activator, 100 nM) for 24 hours to evaluate the response of Hedgehog signaling. Stemness marker expression (Nanog, Sox2, Bmi1, Oct4) was measured using qRT-PCR. The combination index (CI) for GANT61 with trastuzumab was calculated using CompuSyn software to determine synergistic doses (CI < 1). The effects of these doses on stemness markers were assessed. Data were analyzed using two-way ANOVA and Tukey’s post hoc test (p < 0.05). Trastuzumab-resistant cells showed upregulated Hedgehog signaling. GANT61 reduced, while SAG21K increased stemness marker expression in both resistant cell lines. The combination of GANT61 with trastuzumab had a synergistic effect, significantly lowering stemness markers. These findings suggest that Hedgehog signaling supports stemness in resistant cells and that targeting this pathway could enhance trastuzumab efficacy. Further research should explore the clinical potential of Hedgehog inhibitors in combination therapies.