Abstract PS2-11-23: Targeting APT-2 against therapy resistance in Breast Cancer

Abstract Breast cancer (BC) is the most dangerous cancers among women. Therapy resistance to thechemotherapy is the most concerning for the breast cancer management. Protein S-palmitoylation is a post-translational reversible modification of some specific proteins whichhelps them to attach to the cell membrane. Depalmitoylation reverses palmitoylation and is catalyzed byenzymes belonging to the a/b hydrolase family of serine hydrolases called acyl protein thioesterases 1/2(APT 1/2). SCRIB, STAT3, TNFR1, ZDHHC6, and MC1R are the known targets of APT-2 and many of themhave established role in cancer progression. APT-2 inhibitor ML349 inhibited soft agar colony formation, 2D clonogenicity of breast cancer cells. ML349 treatment sensitized breast cancer cells toward Doxorubicin both in vitro and invivo. Both treatment with ML349 and siRNA knock down of APT-2 showed suppression of cell cycle regulators, cancer stem cell markers, YAP/TAZ target genes in breast cancer cells. Patient sample data from TCGA shows that lower expression of SCRIB is correlated with increased Overall and Progression free survival of Breast Invasive Ductal Carcinoma, in doxorubicin treated patients. In conclusion, APT-2 inhibition may suppress cancer stemness and therapy resistance in breast cancer cells. Citation Format: A. Jose K, A. Mariya Davis, S. Prabha, K. Dhanura, K. Manu. Targeting APT-2 against therapy resistance in Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-11-23.