PDX: Moving Beyond Drug Screening to Versatile Models for Research Discovery

Abstract

Patient-derived xenografts (PDXs) are tools of the trade for many researchers from all disciplines and medical specialties. Most endocrinologists, and especially those working in oncology, commonly use PDXs for preclinical drug testing and development, and over the last decade large collections of PDXs have emerged across all tumor streams. In this review, we examine how the field has evolved to include PDXs as versatile resources for research discoveries, providing evidence for guidelines and changes in clinical practice.

Keywords: breast cancer; organoid; pathology; patient-derived xenograft; preclinical testing; prostate cancer.

Figure 1.

Utility of patient-derived xenografts for discovery research of hormone-dependent cancers. Collaborations between clinicians and scientists provide access to the high-quality human tumor specimens that are critical for establishing patient-derived xenografts (PDXs). Tumors can be grown as first-generation or one-time PDXs, which are useful for studying the short-term expansion of human tumors; pathology and biomarker expression; the genomic and transcriptomic features of tumors from rare patient cohorts; cellular heterogeneity; and the response of tissues to hormone manipulation and other short-term treatments. Serially transplantable PDXs are useful for drug testing in PDX clinical trials (PCT); identifying mechanism of therapy-resistance that evolve over time; studying intertumor and intratumor heterogeneity; and providing renewable sources of material for explants, organoids, and cultures of conditionally reprogrammed cells. Large collections of serially transplantable PDXs with diverse phenotypes are stored and disseminated by consortia. Altogether, these different uses of PDXs increase the capability and impact of preclinical and translational studies, providing evidence for changing guidelines and improving the clinical management of hormone-dependent cancers.