A patient‐derived explant (<scp>PDE</scp>) model of hormone‐dependent cancer

Margaret M. Centenera, Theresa E. Hickey, Shalini Jindal, Natalie K. Ryan, Preethi Ravindranathan, Hisham Mohammed, Jessica Robinson, Matthew J. Schiewer, Shihong Ma, Payal Kapur,

Molecular Oncology · 2018 · 131 citations · 36 references

DOIFull text

Open access

Concepts

TL;DR

Breast and prostate cancer studies have largely depended on cell lines or xenografts, but these models suffer from low engraftment rates, long development times, and high costs, prompting the search for more clinically relevant alternatives. This study shows that patient‑derived explants (PDEs) from freshly resected tumors preserve native architecture, microenvironment, viability, and oncogenic drivers, enabling high‑throughput, cost‑effective drug testing and genomic analysis that could advance personalized medicine.

Abstract

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 ( PDE s), 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.

References

36