1. Could targeting the protein DNA-PKcs prevent the spread of prostate cancer?
In this study, Goodwin et al. aimed to determine the molecular basis of DNA-PKcs function and the contribution of DNA-PKcs-mediated transcriptional regulation on tumour phenotypes. The DNA-dependent protein kinase (DNA-PK) is composed of two units, including a catalytic subunit (DNA-PKcs) that plays an important role in the DNA damage response and maintenance of genomic stability. This research, which was carried out in the United States, involved mouse models and clinical analysis of tumour samples from 232 patients. Samples were obtained using a case-cohort study design to randomly sample 20% of patients for analysis, in addition to all in whom metastases developed, from a cohort of 1,010 high-risk men who underwent radical prostatectomy between 2000 and 2006.
The authors identified DNA-PKcs as a key contributor to metastatic progression, and the findings support a model wherein the transcriptional regulatory functions of DNA-PKcs induce a signalling program that drives tumour metastases and lethal disease. Dr Iain Frame, director of research at Prostate Cancer UK said “Getting to grips with how and why cancer cells spread around the body is one of the biggest challenges we face today. The answer to this question will allow us to not only predict which early stage prostate cancers may go on to spread and become dangerous, but also develop new treatments to stop the cells spreading in the first place. Although this research could provide us with some of the answers we desperately need, it's still early days. We look forward to further results of this trial and hope they lead to better ways to prevent and treat advanced prostate cancer.”