Gene expression analysis of prostate cancer cells resistant to CDK7 inhibitors

CDK7 has emerged as a cancer target because of its pivotal roles in cell cycle progression and transcription. Several small molecule CDK7 inhibitors (CDK7i) are now in clinical evaluation. Identifying patients most likely to respond to treatment and early detection of tumour evolution towards resistance, are necessary for optimal implementation of cancer therapies. Continuous culturing of prostate cancer cells with Samuraciclib, an ATP-competitive/non-covalent CDK7i, led to outgrowth of resistant cells. RNA-seq expression analysis was undertaken to identify changes in gene expression, revealing acquistion of a mutation, c.289G>A in the CDK7 gene, causing the p.Asp97Asn change. Overall design: To model acquired resistance in cancer, we cultured 22Rv1 prostate cancer cells in culture medium containing 500nM of Samuraciclib for 4 months. To investigate transcriptomic changes in Samuraciclib-resistant cells, RNA-seq was performed using 6 bioreplicates of RNA prepared from 22Rv1 Samuraciclib-resistant cells (SAMRES) and parental 22Rv1 cells (SAMSEN).