O140: How clinically relevant are prostate cancer cell lines? A comprehensive multiomics analysis.

Abstract Introduction Cell lines remain a heavily used resource in cancer research despite their questionable clinical relevance, mainly due to their feasibility and affordability. A range of in silico, in vivo and ex vivo approaches are gaining popularity to potentially replace cell lines, however, we cannot ignore the plethora of historical data from cell lines, nor write off their future use. Therefore, we question if and how cell lines hold clinical relevance. Methods The clinical characteristics of 45 PCa cell lines were compared against worldwide data and the biological features of seven cell lines were compared to over 10,000 well-characterised cases from 23 studies in eight countries. Clinical comparisons included age, race, Gleason grade, cancer type and multiomics variables included mutations, copy number alterations, structural variants, microsatellite instability, mRNA and protein expression, and tumour mutational burden. Using this, cell-line-like patients were identified and characterised. Results The most used cell lines were derived from metastases over 40 years ago and accurately represented very few patients. The most common alterations in clinical datasets were not necessarily altered in cell lines and 24% of key PCa gene alterations were not altered in any cell line. From the seven cell lines analysed, the greatest number of patients were found to be biologically similar to VCaP. Conclusion Cell lines are valuable in cancer research, but they must hold biological and clinical relevance. PCa cell lines should either be applicable to typical PCa patients or representative of specific cancer subtypes to increase the relevance of translational research.