Heterogeneous Responses to Combination Therapy of Anti-AR Antagonists and mTORi: Analysis of Gene Expression Profiles Across Prostate Cancer Cell Lines

Background: Combination therapies targeting different pathways, such as mTOR inhibitors and AR antagonists, have been explored for treating castration-independent prostate cancer. However, their success has been limited. Materials and Methods: Four prostate cancer cell lines with varying metastatic potential were analyzed for sensitivity to combination therapy using proliferation, western blot, and viability assays. Gene set expression profiles were compared to identify correlations with drug sensitivity. Gene set enrichment profiles of malignant versus benign cell lines were also analyzed using CCLE data. Results: The cell lines showed varying sensitivity to the combination therapy, which correlated with distinct gene expression and enrichment profiles. These patterns were linked to drug resistance and metastatic potential. Additionally, several genes were identified as promising therapeutic targets for prostate cancer. Conclusions: This study demonstrates significant heterogeneity in drug resistance and metastatic potential among prostate cancer cell lines. Unique gene expression patterns linked to these characteristics were identified, providing insights for developing targeted therapies and advancing prostate cancer treatment.