Investigating the role of LRP1B in chemo-resistance in advanced triple-negative breast cancer.

Abstract

e13150 Background: Advanced triple-negative breast cancer is usually chemo-resistant with high mortality. We aimed to develop novel therapeutic strategies to overcome chemo-resistance in triple-negative breast cancer. Methods: Patient-Derived Organoids (PDOs) of triple-negative breast cancer were used for Whole-Exome Sequencing (WES) and drug screening. The HS578T cell line with the highest expression of LRP1B was transfected with LRP1B targeted siRNA and followed by cell cycle analysis, RNA-seq, etc. Apoptotic cell detection was performed after treatment with cisplatin and paclitaxel drugs on HS578T cells with LRP1B gene knockdown. Results: Through WES and drug screening in triple-negative breast cancer Patient-derived organoids (PDOs), we found that PDOs with low expression of LRP1B were resistant to paclitaxel and cisplatin. Additionally, PDOs with low expression of LRP1B exhibited resistance to cell cycle-specific drugs such as vinorelbine and gemcitabine. After being transfected with LRP1B-targeted siRNA, TNBC cells were arrested in the G0/G1 cell cycle phase and showed resistance to paclitaxel chemotherapy drugs. RNA-seq profiling revealed that KD LRP1B leads to the downregulation of genes related to pathways of fatty acid metabolism and G2/M checkpoint. Conclusions: Targeting LRP1B potentially offers new insights for reversing paclitaxel resistance in advanced triple-negative breast cancer.