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.

Immunotherapeutic Strategies for the Treatment of Glioblastoma: Current Challenges and Future Perspectives

“…Moreover, a better understanding of GBM tumor biology, in terms of local TME immunosuppression and systemic T cell dysfunction, is essential in the development of more targeted therapies. Recent advances in patient-derived GBM xenografts in humanized and immunotolerant murine models, as well as in ex vivo 3-D systems and microfluidics, can assist researchers in studying the intricate relationship between GBM and immune cells, leading to the discovery of new ways to efficiently modulate it [371]. Furthermore, these models serve as excellent preclinical settings for the high-throughput screening of therapeutic agents in a time-efficient and cost-effective manner.…”