A patient-derived explant (PDE) model of hormone-dependent cancer

Breast and prostate cancer research to date has largely been predicated on the use of cell lines in vitro or in vivo. These limitations have led to the development of more clinically relevant models, such as organoids or murine xenografts that utilize patient-derived material; however, issues related to low take rate, long duration of establishment, and the associated costs constrain use of these models. This study demonstrates that ex vivo culture of freshly resected breast and prostate tumor specimens obtained from surgery, termed patient-derived explants (PDEs), provides a high-throughput and cost-effective model that retains the native tissue architecture, microenvironment, cell viability, and key oncogenic drivers. The PDE model provides a unique approach for direct evaluation of drug responses on an individual patient's tumor, which is amenable to analysis using contemporary genomic technologies. The ability to rapidly evaluate drug efficacy in patient-derived material has high potential to facilitate implementation of personalized medicine approaches.Margaret M. Centenera, Theresa E. Hickey, Shalini Jindal, Natalie K. Ryan, Preethi Ravindranathan, Hisham Mohammed, Jessica L. Robinson, Matthew J. Schiewer, Shihong Ma, Payal Kapur, Peter D. Sutherland, Clive E. Hoffmann, Claus G. Roehrborn, Leonard G. Gomella, Jason S. Carroll, Stephen N. Birrell, Karen E. Knudsen, Ganesh V. Raj, Lisa M. Butler, Wayne D. Tille

The progression of benign prostatic hyperplasia: examining the evidence and determining the risk.

BACKGROUND: Benign prostatic hyperplasia (BPH) is often associated with enlargement of the prostate gland, lower urinary tract symptoms, decreased urinary flow and a reduced quality of life. Furthermore, if the symptoms associated with BPH are left untreated, serious complications, such as acute urinary retention, may ensue. Evidence is emerging from long-term clinical studies to suggest that BPH is a progressive disease, with some patients progressing much more rapidly than others. OBJECTIVE: This article aims to explore the natural history of BPH progression from a molecular, pathological and clinical perspective, with emphasis on the key clinical evidence to support the progressive nature of this disease. How our increased understanding of the disease and of the risk factors for BPH progression might be applied to improve current management practices are also discussed. CONCLUSION: Strategies to identify patients most at risk and guidelines directed towards long-term management, in addition to short-term treatment, may be useful in helping to prevent BPH progression