Whole-exome sequencing of parental and radioresistant human cell line models of prostate cancer
Background: Radiotherapy (RT) is an essential tool in the management of prostate cancer. Response to RT varies, with 20-40% of patients developing radioresistance. However, the effects of RT (i.e., whether the cancer is responding or not) are typically detectable only towards the end of treatment. The inability to readily identify unresponsive patients means they are exposed to co-morbidities and side effects, clinical resources are wasted and, importantly, there is a delay in the introduction of other therapies, which can contribute to tumour progression. Purpose: This project followed a multiomics approach to identify better biomarkers of radioresistance. These surrogates could monitor RT response and help identify in a timely manner those patients whose cancers do not respond to RT, thus helping to improve their management and outcomes.  Experimental design: With this goal, radioresistant (RR) models were developed from two well-established human prostate cancer cell line models: DU145 and PC3. Cells from parental and RR models were collected and DNA was extracted for whole-exome sequencing (WES).  Results: Mutation data from WES was used alongside other multiomics datasets for selection of candidate biomarkers. 28 potential surrogates of RR were identified, with 4 top candidates showing particular promise due to being functionally related to resistance, upregulated in RR models and likely vesicle-bound.