Generation, evolution, interfering factors, applications, and challenges of patient-derived xenograft models in immunodeficient mice

Abstract

Establishing appropriate preclinical models is essential for cancer research. Evidence suggests that cancer is a highly heterogeneous disease. This follows the growing use of cancer models in cancer research to avoid these differences between xenograft tumor models and patient tumors. In recent years, a patient-derived xenograft (PDX) tumor model has been actively generated and applied, which preserves both cell–cell interactions and the microenvironment of tumors by directly transplanting cancer tissue from tumors into immunodeficient mice. In addition to this, the advent of alternative hosts, such as zebrafish hosts, or in vitro models (organoids and microfluidics), has also facilitated the advancement of cancer research. However, they still have a long way to go before they become reliable models. The development of immunodeficient mice has enabled PDX to become more mature and radiate new vitality. As one of the most reliable and standard preclinical models, the PDX model in immunodeficient mice (PDX-IM) exerts important effects in drug screening, biomarker development, personalized medicine, co-clinical trials, and immunotherapy. Here, we focus on the development procedures and application of PDX-IM in detail, summarize the implications that the evolution of immunodeficient mice has brought to PDX-IM, and cover the key issues in developing PDX-IM in preclinical studies.

Patient Characteristics Associated with Growth of Patient-Derived Tumor Implants in Mice (Patient-Derived Xenografts)

“…In GBM, in a study by Sloan et al [45,46], 69 samples from patients with glioblastoma multiforme were collected for PDX generation, achieving successful engraftment in 37 implanted samples in mice. Interestingly, tumor growth rate was measured between passages, and confirmed to be progressively higher, with 11 samples (15.9%) reaching 40% or more increase in tumor growth rate between the first and third passages [47].…”

“…More specifically, from the histology standpoint, Ki67% protein expression positivity in tumor tissue, tumor grade of differentiation, and the presence of lymphovascular and neural invasion in sample of origin were statistically correlated with a higher engraftment success rate. All these markers have previously been associated with bad prognosis in different types of cancers [47][48][49][50][51][52]. Ki67% protein expression, a marker measured in most kinds of cancers and considered decisive for therapy in some, like breast cancer, has previously been correlated with a higher engraftment success rates, and has been used in a model for prediction of PDX establishment in the previous literature [53,54].…”