biostudies-literatureUnknown26(22)Batten SMetastatic castration-resistant prostate cancer/PCa (mCRPC) is a clinically advanced form of PCa that is associated with increased aggressiveness, cancer stemness, morbidity, and the risk of developing resistance to taxanes, currently the first-line chemotherapy for mCRPC. Clofazimine (CLF) is a potential immunomodulator drug that is FDA-approved for the treatment of leprosy. Recently, using <i>in vitro</i>, <i>in vivo</i>, and <i>ex vivo</i> models, we established the efficacy of CLF in chronic myeloid leukemia and multiple myeloma. Here, we demonstrate that CLF is effective as a single agent and in combination with taxanes in a panel of cell lines representing the diversity of CRPC patients. Using a microfluidic assay, we showed the impact of CLF on cancer cell migration and metastatic potential. Further, we also found that CLF reduces ALDH activity-a marker for cancer 'stem-like' cells (CSCs), a subtype of cancer cells with self-renewal and differentiation capacities (epithelial-to-mesenchymal transdifferentiation/EMT). Bulk and single-cell RNAseq followed by functional validation and <i>in silico</i> analysis showed that CLF treatment is associated with apoptosis, ER stress, oxidative phosphorylation, and mitochondrial dysfunction. Most importantly, CLF modulates the expression of several non-coding RNAs, including MALAT1 and NEAT1, that are linked to tumor cell proliferation, cell migration, and drug resistance.International journal of molecular sciences10892https://www.ebi.ac.uk/biostudies/studies/S-EPMC12652201biostudies-literatureClofazimine Treatment Modulates Key Non-Coding RNAs Associated with Tumor Progression and Drug Resistance in Lethal Prostate Cancer.PMC12652201Pfitzer JKumar HBatten SArnold RDNweze DCMazumder SMistriotis PMitra Ghosh TMitra AKfalseClofazimine Treatment Modulates Key Non-Coding RNAs Associated with Tumor Progression and Drug Resistance in Lethal Prostate Cancer.Metastatic castration-resistant prostate cancer/PCa (mCRPC) is a clinically advanced form of PCa that is associated with increased aggressiveness, cancer stemness, morbidity, and the risk of developing resistance to taxanes, currently the first-line chemotherapy for mCRPC. Clofazimine (CLF) is a potential immunomodulator drug that is FDA-approved for the treatment of leprosy. Recently, using <i>in vitro</i>, <i>in vivo</i>, and <i>ex vivo</i> models, we established the efficacy of CLF in chronic myeloid leukemia and multiple myeloma. Here, we demonstrate that CLF is effective as a single agent and in combination with taxanes in a panel of cell lines representing the diversity of CRPC patients. Using a microfluidic assay, we showed the impact of CLF on cancer cell migration and metastatic potential. Further, we also found that CLF reduces ALDH activity-a marker for cancer 'stem-like' cells (CSCs), a subtype of cancer cells with self-renewal and differentiation capacities (epithelial-to-mesenchymal transdifferentiation/EMT). Bulk and single-cell RNAseq followed by functional validation and <i>in silico</i> analysis showed that CLF treatment is associated with apoptosis, ER stress, oxidative phosphorylation, and mitochondrial dysfunction. Most importantly, CLF modulates the expression of several non-coding RNAs, including MALAT1 and NEAT1, that are linked to tumor cell proliferation, cell migration, and drug resistance.2025-01-01T00:00:00Z2025 Nov2026-06-05T03:16:37.211Z2026-06-05T03:06:53.547ZS-EPMC126522014130337810.3390/ijms262210892