Preclinical Models and Technologies in Glioblastoma Research: Evolution, Current State, and Future Avenues

Abstract

Glioblastoma is the most common malignant primary central nervous system tumor and one of the most debilitating cancers. The prognosis of patients with glioblastoma remains poor, and the management of this tumor, both in its primary and recurrent forms, remains suboptimal. Despite the tremendous efforts that are being put forward by the research community to discover novel efficacious therapeutic agents and modalities, no major paradigm shifts have been established in the field in the last decade. However, this does not mirror the abundance of relevant findings and discoveries made in preclinical glioblastoma research. Hence, developing and utilizing appropriate preclinical models that faithfully recapitulate the characteristics and behavior of human glioblastoma is of utmost importance. Herein, we offer a holistic picture of the evolution of preclinical models of glioblastoma. We further elaborate on the commonly used in vitro and vivo models, delving into their development, favorable characteristics, shortcomings, and areas of potential improvement, which aids researchers in designing future experiments and utilizing the most suitable models. Additionally, this review explores progress in the fields of humanized and immunotolerant mouse models, genetically engineered animal models, 3D in vitro models, and microfluidics and highlights promising avenues for the future of preclinical glioblastoma research.

Keywords: 3D models; animal models; cell lines; genetic engineering; glioblastoma; microfluidics; preclinical models.

Figure 1

Illustration representing the different in vitro models used in glioblastoma research.

Figure 2

Illustration representing the different animal models used for in vivo glioblastoma research, along with the advantages and disadvantages of each.

Figure 3

The different methods used for the generation of animal models of GBM. (A) The implantation of established cell lines into syngeneic animals of the same species allows for the use of immunocompetent hosts. (B) The use of established human cell lines that were initially obtained from patient tumor samples and propagated in culture require implantation into immunocompromised, humanized, or immunotolerant animal models. (C) Similarly, the use of patient-derived xenografts involves the implantation of patient tissue into immunocompromised or humanized/immunotolerant hosts; however, this type of xenografting does not include in vitro passaging as an intermediate step. (D) The genetic engineering of animal embryos or the breeding of genetically engineered parents can produce animal models that develop tumors on their own in a fashion that can be temporally and spatially controlled. (E) In a similar way, the use of viral vectors to transfect animals allows for the generation of tumors “from scratch” in a temporally and spatially controlled manner.