“Castration-persistence” is a distinct state of tolerance to androgen receptor targeting therapies in prostate cancer

Study ID Alternative Stable ID Type
EGAS00001003172 Other

Study Description

Androgen receptor (AR) signalling is important in prostate cancer progression, and therapies that specifically target this pathway are the mainstay of treatment for advanced disease. Treatment however is non-curative, and resistance develops inevitably with time. Although the mechanisms that drive progressive ‘castration resistant’ disease are reasonably well characterized, how tumours survive acute pathway inhibition is unclear. We performed a neo-adjuvant study of a novel combination of AR targeting therapies, and noted that the objective response to treatment was highly variable. To determine what was driving tumour persistence in poorly responding patients, we comprehensively characterised pre- and post-treatment samples were using both whole genome and RNA-sequencing. We find that ‘castration-persistence’ is a distinct state from ‘castration-resistance’, and is mediated by global transcriptional reprogramming leading to transitional EMT state, which is shared with benign luminal epithelial cells. This appears to be AP-1 and KLF driven, and represents and integration ... (Show More)

Study Datasets 1 dataset.

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Dataset ID Description Technology Samples
Aligned whole-genome sequencing and RNA-seq of localised prostate cancer for study 'Loss of SNAI2 in prostate cancer correlates with clinical response to androgen deprivation therapy'.
HiSeq X Ten 109

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