In the September issue of European Urologic Oncology, Shafi et al. published their results of a novel model system to generate prostate cancer patient-derived explants (PDE), which highlight the importance of tumor microenvironment features1. In brief, they demonstrate that stromal factors in the transplanted tumor tissue are maintained in the foreign host and that these desmoplastic indices impact the subsequent responsiveness/dependency of the tumor on androgen receptor targeted therapies. These same stromal factors are not only critical to the survival and growth of tumor cells in a foreign tissue (think also metastasis), but they also drive disease resistance. While their models still come short of creating the kind of bone microenvironment that so commonly characterizes metastatic castration-resistant prostate cancer, they do highlight the importance of these stromal factors in the biology of disease progression. It is a fascinating concept that treatment resistance is not simply a selection process of resistant epithelial cell biology but instead is borne out of the microenvironment milieu. This makes sense when we commonly see incomplete, partial or mixed responses to therapy that many times result in a different metastatic pattern that was originally present when therapy started.
Yes, establishing new prostate cancer tumors explants is hard; it undoubtedly will require a village of factors and conditions that we still may not fully understand. But within that village may lie therapeutic targets to change or halt the process most characteristic of lethal prostate cancer: metastasis.
Written by: Daniel J. George, MD, Medical Oncologist, Professor of Medicine, Professor of Surgery, Duke Cancer Institute, Durham, North Carolina
1. Shafi AA et al. Patient-derived Models Reveal Impact of the Tumor Microenvironment on Therapeutic Response. Eur Urol Oncol. 2018 Sep;1(4):325-337.