The what, when, and why of human prostate cancer xenografts

Background: Presently, ∼85 serially transplantable human prostate cancer xenografts spanning the phenotypic, epigenetic, and genetic heterogeneity seen clinically are available in a variety of laboratories throughout the world. If distributed to the prostate cancer research community, these can provide an experimental platform for resolving the specificity versus generalizability of basic cancer biology principles (eg, credentialing of therapeutic molecular targets) and for validating translational approaches for prevention, diagnosis, and therapy. Thus, there is an urgent need to distribute the already established serially transplantable human prostate cancer xenografts and to develop robust methods for establishing new ones. Methods: To accelerate the development of such additional xenografts, particularly from patients treated with the newer standard of care agents (ie, abiraterone, enzalutamide, cabazitaxel, alpharadin, etc), a historic review of the field will be presented. Results: Over the last 50 years, multiple groups throughout the world have developed methods for the successful establishment of serially transplantable human prostate cancer xenografts using a variety of immune deficient mice. These are summarized chronologically. Conclusions and Future: With the ever growing appreciation of the value of personalized medicine (aka precision medicine), methods need to be developed that allow efficient and timely growth of primary patient derived prostate cancer xenografts (PDXs), which can be used as “avatars” for defining optimal therapy for that specific patient. Such development should be based upon the leads obtained from the successful establishment of serially transplantable prostate cancer xenografts described in this review.