Utility of Glioblastoma Patient-Derived Orthotopic Xenografts in Drug Discovery and Personalized Therapy

Frontiers in Oncology

卷:8

Hatem E. Sabaawy¹  Sharon R. Pine¹  Michele Patrizii²  Monica Bartucci³ 

[1]Department of Medicine, RBHS-Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States

[2]|Graduate Program in Cellular and Molecular Pharmacology, RBHS-Robert Wood Johnson Medical School, Piscataway, NJ, United States

[3]|Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, United States

关键词: glioblastoma;    patient-derived xenografts;    mouse models;    personalized therapy;    precision medicine;   

DOI  :  10.3389/fonc.2018.00023

来源: DOAJ

【 摘 要 】

Despite substantial effort and resources dedicated to drug discovery and development, new anticancer agents often fail in clinical trials. Among many reasons, the lack of reliable predictive preclinical cancer models is a fundamental one. For decades, immortalized cancer cell cultures have been used to lay the groundwork for cancer biology and the quest for therapeutic responses. However, cell lines do not usually recapitulate cancer heterogeneity or reveal therapeutic resistance cues. With the rapidly evolving exploration of cancer “omics,” the scientific community is increasingly investigating whether the employment of short-term patient-derived tumor cell cultures (two- and three-dimensional) and/or patient-derived xenograft models might provide a more representative delineation of the cancer core and its therapeutic response. Patient-derived cancer models allow the integration of genomic with drug sensitivity data on a personalized basis and currently represent the ultimate approach for preclinical drug development and biomarker discovery. The proper use of these patient-derived cancer models might soon influence clinical outcomes and allow the implementation of tailored personalized therapy. When assessing drug efficacy for the treatment of glioblastoma multiforme (GBM), currently, the most reliable models are generated through direct injection of patient-derived cells or more frequently the isolation of glioblastoma cells endowed with stem-like features and orthotopically injecting these cells into the cerebrum of immunodeficient mice. Herein, we present the key strengths, weaknesses, and potential applications of cell- and animal-based models of GBM, highlighting our experience with the glioblastoma stem-like patient cell-derived xenograft model and its utility in drug discovery.

【 授权许可】

Unknown