Microbiome Molecular Charaterisation

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Prostate cancer is the second commonest malignancy in the UK and the second commonest cause of male mortality in the UK. Androgen deprivation therapy remains the mainstay of treatment, not only for advanced prostate cancer but also in the adjuvant and neo-adjuvant settings. Androgen deprivation therapy induces a remission in 80 to 90% of patients with advanced disease and results in a median progression-free survival of 12 to 33 months, at which time an androgen-independent phenotype usually emerges. This accounts for a median overall survival of 23 to 37 months from the initiation of androgen deprivation. Recent preclinical studies have shown that the intestinal microbiota is associated with response to treatments such as platinum chemotherapy (oxaliplatin) \[1\], cyclophosphamide \[2\] and both CTLA-4 blockade \[3\] and anti-PD-L1 \[4\] immunotherapies. Eradication of commensal intestinal flora by antibiotic treatment, or via deriving specific-pathogen-free (SPF) and/or germ-free animals, has been shown to alter the therapeutic efficacy of these agents in tumour models. Intriguingly, a recent study in a melanoma model showed that responses to anti-PD-L1 immunotherapy could be increased by feeding animals a strain of Bifidobacterium - a species commonly used in probiotic supplements - prior to initiating therapy. Collectively, these studies suggest that the composition of the intestinal microbiome is both essential for therapeutic efficacy and a target that could potentially be modulated to enhance treatment response. MMC is a prospective, observational, multi-centre study evaluating prostate cancer biology and associated microbiota. Patients must be willing to undergo a fresh tumour biopsy for molecular analyses. Following consent to MMC, fresh tumour tissue will be sent to designated research laboratories (see laboratory manual) for analyses to identify molecular aberrations and dysbiosis through targeted or broader molecular analyses (e.g. exome, transcriptome, whole genome), as well as (when indicated) orthogonal assays (e.g. immunohistochemistry, immunofluorescence, RNAish, digital droplet PCR). MMC will focus on tumour and microbiota characterisation (both CSPC and mCRPC) with recent studies indicating that this is a highly heterogeneous disease. The data acquired will be made available to patients, when indicated, and their clinical care team to help select what early clinical trial options merit consideration. Patients will not receive any treatment or IMP as part of this MMC protocol. Results of the molecular characterisation and microbiota studies will be made available to the treating investigator and the patient at a study specific visit (telephonic or face-to-face); patients will then be followed up every 6-months via medical notes review or telephone for survival and anti-cancer treatment data.