Patient-Derived Xenograft Models of Prostate Cancer

Abstract

Prostate cancer is the second leading cause of cancer in men in western countries. It is characterized by specific clinical features as androgen responsiveness, hence the initial efficacy of endocrine therapies. Recurrent prostate cancer inevitably progresses toward castration resistance with metastatic spread to the bone, responsible for most of the experienced morbidity. Research into the mechanisms of tumor growth and disease progression have been hampered significantly by the lack of experimental models, as a result of the rarity of spontaneous prostate cancer in other mammals and lack of expertise in growing prostate cancer tissue directly from the patient in a Petri dish or in immune-deficient mice to generate patient-derived xenograft (PDX) models. Major efforts by several research groups worldwide have resulted in the establishment of a substantial set of PDXs. This review highlights advances in the development of prostate cancer PDX models, with an overview of the contemporary sets of prostate cancer PDXs available and their use in experimental and translational research. Several approaches are outlined that aim to improve existing prostate cancer PDXs to better capture the complexity of the disease including orthotopic engraftment procedures, humanization of the immune and endocrine murine system, and efforts to replicate the biological diversity by extending the PDX collections with resistant disease stages. Finally, novel screening approaches, such as co-clinical trials and PDX clinical trials, are being developed that increase preclinical value and enhance translational power of (prostate cancer) PDXs.