- PII
- S19982860S0132342325030034-1
- DOI
- 10.7868/S1998286025030034
- Publication type
- Article
- Status
- Published
- Authors
- Volume/ Edition
- Volume 51 / Issue number 3
- Pages
- 398-407
- Abstract
- Tumor cell death induction via activation of TRAIL (tumor necrosis factor-related apoptosis inducing ligand) cytokine signaling pathway is a promising strategy for anticancer therapy. Previously, we developed a fusion protein SRH-DR5-B-iRGD based on the DR5 (death receptor 5)-specific cytokine TRAIL variant DR5-B with antiangiogenic peptides. The SRH peptide specifically binds to the VEGFR2 (vascular endothelial growth factor receptor 2) receptor and blocks its VEGF-mediated activation; the iRGD peptide binds to integrin avP3 and the NRP-1 (neuropilin-1) receptor. All of these targets are known to be overexpressed on the surface of tumor cells. In the current study, we investigated the cytotoxic activity of the SRH-DR5-B-iRGD fusion protein in comparison with DR5-B in vitro in ovarian and breast adenocarcinoma cell lines with different BRCA mutation status in combination with a targeted poly(ADP-ribose) polymerase (PARP) inhibitor olaparib. Olaparib synergistically enhanced the cytotoxicity of TRAIL-based proteins regardless of the presence of BRCA mutations in the cells, and this effect was more pronounced for SRH-DR5-B-iRGD. Thus, the combination of SRH-DR5-B-iRGD with olaparib can be considered as a new approach to treatment of ovarian and breast adenocarcinomas regardless of the presence of BRCA mutations.
- Keywords
- TRAIL DR5 VEGFR2 интегрин avfβ3 рак яичника рак молочной железы BRCA PARP олапариб
- Date of publication
- 08.12.2025
- Year of publication
- 2025
- Number of purchasers
- 0
- Views
- 9
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