![]() In 1983, Bosma (Fox Chase Cancer Institute, PA, USA) first described the severe combined immunodeficient (SCID) mice that lack both functional T and B lymphocytes. With the introduction of highly immunocompromised mice as recipients, PDX use is now widespread and is becoming a standard “Avatar” model for human cancer research.Ģ.2. This has become an essential tool for preclinical and translational research, particularly for investigations of tumor pathology and for chemotherapeutic drug development. The PDXs are established by direct engraftment of a patient tumor into an immunocompromised mouse, maintaining the tumor growth in vivo. Accordingly, the National Cancer Institute (NCI, MD, USA) recently decided to replace the NCI-60, a panel of 60 human cell lines, with patient-derived xenografts (PDXs) for drug screening. Mice and humans are considerably different, and human cancer cell lines somehow lose their original tumor characteristics when transplanted. Mouse tumors and human-cell-line-transplanted animal models are not always representative of human cancer pathologies, contributing to distinct drug responses. One possible reason is the lack of appropriate human cancer models. This figure is lower for oncology drugs, at approximately 5%. Fewer than 10% of candidate drugs are approved for the market, even if preclinical trials are successful. Preclinical studies using animal models are essential for drug development. A PDX biobank equipped with patients’ clinical data, gene-expression patterns, mutational statuses, tumor tissue architects, and drug responsiveness will be an authoritative resource for developing specific tumor biomarkers for chemotherapeutic predictions, creating individualized therapy, and establishing precise cancer medicine. PDX mice with human hematopoietic and immune systems (humanized PDX) are powerful tools for the analysis of tumor–immune system interaction and evaluation of immunotherapy response. Human hormone treatment is necessary to establish hormone-dependent cancers such as prostate and breast cancers. Subcutaneous transplantation is the most popular method to establish PDX, but some tumors require specific environments, e.g., orthotropic or renal capsule transplantation. ![]() Success rates differ with tumor origin: gastrointestinal tumors acquire a higher engraftment rate, while the rate is lower for breast cancers. The engraftment rate increases with the introduction of Non-obese diabetic Severe combined immunodeficiency (NOD/SCID)-based immunocompromised mice, especially the NK-deficient NOD strains NOD/SCID/interleukin-2 receptor gamma chain(IL2Rγ) null (NOG/NSG) and NOD/SCID/Jak3(Janus kinase 3) null (NOJ). Since a PDX model retains the characteristics of the primary patient tumor including gene expression profiles and drug responses, it has become the most reliable in vivo human cancer model. ![]() Patient-derived xenograft (PDX) models are created by engraftment of patient tumor tissues into immunocompetent mice. ![]()
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