Patient-derived xenografts: a promising resource for preclinical cancer research

Abstract

Patient-derived xenograft tumors retain molecular and histopathological features of the originating tumor and are useful preclinical tools for drug discovery and assessment. We recently reported that 'rapid' engraftment of head and neck squamous cell carcinoma samples is highly prognostic and correlates with deregulation of the G1/S checkpoint. Tumors with genetic alterations in cyclinD1 (CCND1) and/or cyclin-dependent kinase inhibitor 2A (CDKN2A) are more likely to respond to abemaciclib.

Keywords: Patient-derived xenografts; abemaciclib; biomarker discovery; engraftment; head and neck squamous cell carcinoma; preclinical tool.

Figure 1.

Patient-derived xenografts in personalized risk stratification and drug sensitivity screening. Head and neck squamous cell carcinoma (HNSCC) patient tumors that engraft into immuno-compromised mice by 8 weeks (rapid engrafters) have poor clinical outcome. Rapid engraftment can serve as a predictive biomarker to indicate the strong need for a patient to receive aggressive therapy (radiation and/or chemotherapy). Thus, engraftment status can be added to the existing pathological and clinical features used to decide the course of treatment. Given the rapid growth of these patient-derived xenografts (PDXs), they can be treated and tested quickly with approved drugs (X, Y, Z) to determine which one provides the highest tumor response and then applied to the patient. As extensive numbers of PDXs are tested, the heterogeneous landscape of mutations and their responses to various drugs will be captured with the goal that these molecular profiles can be used in the future, directly on patient tumors, to determine prognosis and predictive therapies (gray dashed arrows). Abbreviations: PDX = patient-derived xenograft.