Creating a potential diagnostic for prostate cancer risk stratification (InformMDx™) by translating novel scientific discoveries concerning cAMP degrading phosphodiesterase-4D7 (PDE4D7)

Henderson, Dave J.P. and Houslay, Miles D. and Bangma, Chris H. and Hoffmann, Ralf (2019) Creating a potential diagnostic for prostate cancer risk stratification (InformMDx™) by translating novel scientific discoveries concerning cAMP degrading phosphodiesterase-4D7 (PDE4D7). Clinical Science, 133 (2). pp. 269-286. ISSN 0143-5221

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    Abstract

    Increased PSA-based screening for prostate cancer has resulted in a growing number of diagnosed cases. However, around half of these are ‘indolent’, neither metastasizing nor leading to disease specific death. Treating non-progressing tumours with invasive therapies is currently regarded as unnecessary over-treatment with patients being considered for conservative regimens, such as active surveillance (AS). However, this raises both compliance and protocol issues. Great clinical benefit could accrue from a biomarker able to predict long-term patient outcome accurately at the time of biopsy and initial diagnosis. Here we delineate the translation of a laboratory discovery through to the precision development of a clinically validated, novel prognostic biomarker assay (InformMDx™). This centres on determining transcript levels for phosphodiesterase-4D7 (PDE4D7), an enzyme that breaks down cyclic AMP, a signalling molecule intimately connected with proliferation and androgen receptor function. Quantifiable detection of PDE4D7 mRNA transcripts informs on the longitudinal outcome of post-surgical disease progression. The risk of post-surgical progression increases steeply for patients with very low ‘PDE4D7 scores’, while risk decreases markedly for those patients with very high ‘PDE4D7 scores’. Combining clinical risk variables, such as the Gleason or CAPRA (Cancer of the Prostate Risk Assessment) score, with the ‘PDE4D7 score’ further enhances the prognostic power of this personalized, precision assessment. Thus the ‘PDE4D7 score’ has the potential to define, more effectively, appropriate medical intervention/AS strategies for individual prostate cancer patients.