Establishment of a Patient-Derived Tumor Xenograft Model and Application for Precision Cancer Medicine

摘要

Patient-derived xenograft (PDX) models can be created with the transplantation of cancerous cells or tissues from patients’ primary tumors into immunodeficient mice. PDXs are now in the spotlight as more accurate human cancer models compared with mouse tumor and human cancer cell lines transplanted into mice. PDX technology leads to breakthroughs with the introduction of novel, highly immunodeficient mice such as NOG (NOD/Scid/IL2Rγnull), NSG (NOD/Scid/IL2Rγnull), and NOJ (NOD/Scid/Jak3null) mice. Xenograft efficiency differs by type of tumor, site of implantation, and tumor aggressiveness. Subcutaneous implantation is a standard method for PDX, and renal capsule or orthotropic implantation improves the efficiency. Despite positive test results in animal cancer models, significant numbers of novel drug candidates fail in clinical trials because conventional animal models such as murine tumor and human cancer cell line transplantation models do not always reflect the nature of human cancers. Since PDXs conserve the original tumor characteristics such as heterogeneous histology, clinical biomolecular signatures, malignant phenotypes and genotypes, tumor architecture, and tumor vasculature, they are currently believed to offer relevant predictive insights into clinical outcomes when evaluating the efficacy of novel cancer therapies. PDX banks with integrated genomic signatures are now established in many organizations including pharmaceutical companies. These PDX databases are becoming powerful tools for advancing precision cancer medicine.