Generation of Prostate Cancer Patient-Derived Xenografts to Investigate Mechanisms of Novel Treatments and Treatment Resistance.

Treatment advances lead to survival benefits of patients with advanced prostate cancer. These treatments are highly efficacious in a subset of patients; however, similarly to other cancers, after initial responses the tumors develop resistance (acquired resistance) and the patients succumb to the disease. Furthermore, there is a subset of patients who do not respond to the treatment at all (de novo resistance). Preclinical testing using patient-derived xenografts (PDXs) has led to successful drug development, and PDXs will continue to provide valuable resources to generate clinically relevant data with translational potential. PDXs demonstrate tumor heterogeneity observed in patients, preserve tumor-microenvironment architecture, and provide clinically relevant treatment responses. In view of the evolving biology of the advanced prostate cancer associated with new treatments, PDXs representing these new tumor phenotypes are urgently needed for the study of treatment responses and resistance. In this chapter, we describe methodologies used to establish prostate cancer PDXs and use of these PDXs to study de novo and acquired resistance.