Abstract 7918: Suppression of MAGED1 increases sensitivity to PARP inhibitor in BRCA-mutated breast cancer cells

Abstract Background: MAGED1 (Melanoma Antigen Gene Family, Member D1) is a member of the MAGE gene family and is known to be involved in various cellular processes such as cell death, cell cycle regulation, and differentiation. Furthermore, previous studies indicate that MAGED1 is essential for double-strand break (DSB) repair via homologous recombination repair (HRR), and reduced MAGED1 expression sensitizes cancer cells to DNA-damaging agents. This study aimed to investigate the role of MAGED1 in HRR in triple-negative breast cancer (TNBC) and BRCA1/2 mutant breast cancer. Methods: In this study, we validated the function of MAGED1 in HRD using siRNA in triple-negative breast cancer (TNBC) and BRCA-mutated breast cancer cell lines. Cell viability was assessed using CytoFLEX after treating Hs578T, HCC-1937 (BRCA1 5382insC), and BT-474 (BRCA2 c.0391C>A) breast cancer cell lines with cisplatin 200 μM, olaparib 200 μM, and niraparib 50 μM, respectively. Cells were transfected with control siRNA (si-Cont) or two independent siRNAs targeting MAGED1 (si-MAGED1 #1, si-MAGED1 #2). Result: Using cytoFLEX flow cytometry, we investigated siRNA-mediated MAGED1 suppression in BRCA1/2 mutant breast cancer cell lines HCC-1937 (BRCA1 5382insC) and BT-474 (BRCA2 c.0391C>A) exhibited increased sensitivity compared to normal breast cells MCF10A and breast cancer cell lines MCF7 (luminal A) and Hs578T (TNBC). Furthermore, the platinum-based anticancer drug cisplatin was found not to affect MAGED1 inhibition, and the synergistic effect of PARP inhibitors on MAGED1 inhibition was more pronounced in BRCA-mutant cell lines. Additional studies involving RNF8, BARD1, RAD51, and ATM are underway to further elucidate the roles of HRD and MAGED1. Conclusions: Our study demonstrates that silencing of MAGED1 enhances sensitivity to PARP inhibitors in BRCA1/2-mutant breast cancer cell lines. These results suggest that MAGED1 is involved in HRD and could be a therapeutic target to enhance PARP inhibitor response in breast cancer. Citation Format: In Hee Lee, Soo Jung Lee, Byeongju Kang, Jeeyeon Lee, Ho Yong Park, Joon Suk Moon, Ji-Young Park, Yee Soo Chae, Eun Ae Kim, Seol-Hwa Jeong, Jieun Kang. Suppression of MAGED1 increases sensitivity to PARP inhibitor in BRCA-mutated breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7918.