Cancer Res Treat.  2018 Jan;50(1):1-10. 10.4143/crt.2017.307.

The Generation and Application of Patient-Derived Xenograft Model for Cancer Research

• Jung J
• Seol HS
• Chang S

• KMID: 2403469
• DOI: http://doi.org/10.4143/crt.2017.307

Abstract

Establishing an appropriate preclinical model is crucial for translational cancer research. The most common way that has been adopted by far is grafting cancer cell lines, derived from patients. Although this xenograft model is easy to generate, but has several limitations because this cancer model could not represent the unique features of each cancer patient sufficiently. Moreover, accumulating evidences demonstrate cancer is a highly heterogeneous disease so that a tumor is comprised of cancer cells with diverse characteristics. In attempt to avoid these discrepancies between xenograft model and patients' tumor, a patient-derived xenograft (PDX) model has been actively generated and applied. The PDX model can be developed by the implantation of cancerous tissue from a patient's tumor into an immune-deficient mouse directly, thereby it preserves both cell-cell interactions and tumor microenvironment. In addition, the PDX model has shown advantages as a preclinical model in drug screening, biomarker development and co-clinical trial. In this review, we will summarize the methodology and applications of PDX in detail, and cover critical issues for the development of this model for preclinical research.

Keyword

Patient derived xenograft; Preclinical model; Immune deficient mouse; Personalized medicine

MeSH Terms

Animals
Cell Line
Drug Evaluation, Preclinical
Heterografts*
Humans
Mice
Precision Medicine
Transplants
Tumor Microenvironment

Figure

• 

  Fig. 1. An overall procedure for the generation of patient-derived xenograft (PDX) model. The PDX model can be developed by the implantation of fragments from a patient’s tumor into an immunodeficient mouse directly. A part of tumor from surgery (breast or pancreatic tumor in this example) is put in preserving media and the tumor is sliced into small fragments. The fragments are implanted subcutaneously or into the orthotopical organ, for example, mammary fat pad in the case of breast cancer.

• 

  Fig. 2. A flowchart showing the establishment of personalized medicine using patient-derived xenograft (PDX) model. Genomic signature of a primary tumor is analyzed by next-generation sequencing. At the same time, tumor fragments are implanted into immunodeficient mouse. The patient will be treated with the drug that showed best response in PDX. Also, a database of integrated genomic signature would be established to predict a drug response for a new patient with similar genomic signature. SNP, single nucleotide polymorphism.

Reference

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