Sub-Saharan African Prostate Cancer Patient-Derived Cell Lines and High-Throughput Drug Screening: Addressing Ancestry Underrepresentation in Oncobiology Research.

Background/Objectives: Prostate cancer (PC) exhibits marked disparities in incidence and mortality across ethnicities, with men of Sub-Saharan African (SSA) ancestry experiencing 1.7 and 2.0 times higher values, respectively, than European men (EUR). However, SSA preclinical models remain scarce (just one commercial cell line). In this study, we established and characterized a novel panel of PC cell lines derived from SSA patients using conditional reprogramming (CR), a method that enables efficient propagation of primary cells while maintaining their genotypic and phenotypic features. Methods: CR was applied to five SSA-PC samples, and successfully propagated samples were authenticated by STR and ~1 million SNP profiling, and extensively characterized for proliferative capacity, migratory behaviour, karyotyping and epithelial and prostate tumour lineage markers. To explore drug response profiles, a high-throughput screen (HTS) of 1280 clinically annotated compounds was conducted. Results: Three SSA-PC cell lines were successfully established and authenticated, and five potential drug hits were validated. A new finding was the reduced sensitivity of SSA-derived models (9.0 times difference compared to commercial EUR PC cell lines) to camptothecin, a TOP1 inhibitor, while being equally sensitive to epirubicin hydrochloride, a TOP2 inhibitor. The cardiac glycoside digoxin, anthelmintic pyrvinium pamoate and antirheumatic agent auranofin were also efficient drugs in the in vitro testing. Conclusions: These results support the relevance of SSA-derived PC models for preclinical drug screening and highlight the value of including ancestry-diverse models in oncobiology research.