scholarly journals Mouse Models of Glioblastoma for the Evaluation of Novel Therapeutic Strategies

2021 ◽  
Author(s):  
Alexander F Haddad ◽  
Jacob S Young ◽  
Dominic Amara ◽  
Mitchel S Berger ◽  
David R Raleigh ◽  
...  
Keyword(s):  
Mouse Models ◽  
Standard Of Care ◽  
Therapeutic Strategies ◽  
Genetically Engineered ◽  
Genetically Engineered Mouse Models ◽  
Advantages And Disadvantages ◽  
Developmental Therapeutics ◽  
Xenograft Models ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Abstract Glioblastoma (GBM) is an incurable brain tumor with a median survival of approximately 15 months despite an aggressive standard of care that includes surgery, chemotherapy, and ionizing radiation. Mouse models have advanced our understanding of GBM biology and the development of novel therapeutic strategies for GBM patients. However, model selection is crucial when testing developmental therapeutics, and each mouse model of GBM has unique advantages and disadvantages that can influence the validity and translatability of experimental results. To shed light on this process, we discuss the strengths and limitations of 3 types of mouse GBM models in this review: syngeneic models, genetically engineered mouse models (GEMMs), and xenograft models, including traditional xenograft cell lines and patient-derived xenograft (PDX) models.

scholarly journals Biological intratumoral therapy for the high-grade glioma part I: intratumoral delivery and immunotoxins

CNS Oncology ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. CNS38 ◽  
Author(s):  
Joshua Loya ◽  
Charlie Zhang ◽  
Emily Cox ◽  
Achal S Achrol ◽  
Santosh Kesari
Keyword(s):  
Translational Research ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
Therapeutic Strategies ◽  
High Grade ◽  
Major Focus ◽  
Microsurgical Resection ◽  
Intratumoral Delivery ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Management of high-grade gliomas remains a complex challenge. Standard of care consists of microsurgical resection, chemotherapy and radiation, but despite these aggressive multimodality therapies the overall prognosis remains poor. A major focus of ongoing translational research studies is to develop novel therapeutic strategies that can maximize tumor cell eradication while minimizing collateral side effects. Particularly, biological intratumoral therapies have been the focus of new translational research efforts due to their inherent potential to be both dynamically adaptive and target specific. This two-part review will provide an overview of biological intratumoral therapies and summarize key advances and remaining challenges in intratumoral biological therapies for high-grade glioma. Part I focuses on discussion of the concepts of intratumoral delivery and immunotoxin therapies.

scholarly journals NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ganapati V Hegde ◽  
Cecile de la Cruz ◽  
Jennifer M Giltnane ◽  
Lisa Crocker ◽  
Avinashnarayan Venkatanarayan ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Therapeutic Strategies ◽  
Genetically Engineered ◽  
Squamous Cell Carcinomas ◽  
Transcriptional Program ◽  
Squamous Differentiation ◽  
Genetically Engineered Mouse Models ◽  
Downstream Effectors ◽  
Xenograft Models

Squamous cell carcinomas (SCCs) account for the majority of cancer mortalities. Although TP63 is an established lineage-survival oncogene in SCCs, therapeutic strategies have not been developed to target TP63 or it’s downstream effectors. In this study we demonstrate that TP63 directly regulates NRG1 expression in human SCC cell lines and that NRG1 is a critical component of the TP63 transcriptional program. Notably, we show that squamous tumors are dependent NRG1 signaling in vivo, in both genetically engineered mouse models and human xenograft models, and demonstrate that inhibition of NRG1 induces keratinization and terminal squamous differentiation of tumor cells, blocking proliferation and inhibiting tumor growth. Together, our findings identify a lineage-specific function of NRG1 in SCCs of diverse anatomic origin.

scholarly journals SEMMs: Somatically Engineered Mouse Models. A New Tool for In Vivo Disease Modeling for Basic and Translational Research

2021 ◽  
Vol 11 ◽  
Author(s):  
Anthony Lima ◽  
Danilo Maddalo
Keyword(s):  
Mouse Models ◽  
Disease Modeling ◽  
Genetically Engineered ◽  
Response To Therapy ◽  
Preclinical Models ◽  
Screening Programs ◽  
Genetically Engineered Mouse Models ◽  
Direct Mutation ◽  
Xenograft Models

Most experimental oncology therapies fail during clinical development despite years of preclinical testing rationalizing their use. This begs the question of whether the current preclinical models used for evaluating oncology therapies adequately capture patient heterogeneity and response to therapy. Most of the preclinical work is based on xenograft models where tumor mis-location and the lack of the immune system represent a major limitation for the translatability of many observations from preclinical models to patients. Genetically engineered mouse models (GEMMs) hold great potential to recapitulate more accurately disease models but their cost and complexity have stymied their widespread adoption in discovery, early or late drug screening programs. Recent advancements in genome editing technology made possible by the discovery and development of the CRISPR/Cas9 system has opened the opportunity of generating disease-relevant animal models by direct mutation of somatic cell genomes in an organ or tissue compartment of interest. The advent of CRISPR/Cas9 has not only aided in the production of conventional GEMMs but has also enabled the bypassing of the construction of these costly strains. In this review, we describe the Somatically Engineered Mouse Models (SEMMs) as a new category of models where a specific oncogenic signature is introduced in somatic cells of an intended organ in a post-natal animal. In addition, SEMMs represent a novel platform to perform in vivo functional genomics studies, here defined as DIVoS (Direct In Vivo Screening).

scholarly journals Mouse Models in Meningioma Research: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3712
Author(s):  
Julien Boetto ◽  
Matthieu Peyre ◽  
Michel Kalamarides
Keyword(s):  
Mouse Models ◽  
Drug Testing ◽  
Genetically Engineered ◽  
Genetically Engineered Mouse Models ◽  
Disease Mechanisms ◽  
Human Meningiomas ◽  
Genetic Level ◽  
Xenograft Models ◽  
Mouse Models Of Cancer ◽  
Innovative Drugs

Meningiomas are the most frequent primitive central nervous system tumors found in adults. Mouse models of cancer have been instrumental in understanding disease mechanisms and establishing preclinical drug testing. Various mouse models of meningioma have been developed over time, evolving in light of new discoveries in our comprehension of meningioma biology and with improvements in genetic engineering techniques. We reviewed all mouse models of meningioma described in the literature, including xenograft models (orthotopic or heterotopic) with human cell lines or patient derived tumors, and genetically engineered mouse models (GEMMs). Xenograft models provided useful tools for preclinical testing of a huge range of innovative drugs and therapeutic options, which are summarized in this review. GEMMs offer the possibility of mimicking human meningiomas at the histological, anatomical, and genetic level and have been invaluable in enabling tumorigenesis mechanisms, including initiation and progression, to be dissected. Currently, researchers have a range of different mouse models that can be used depending on the scientific question to be answered.

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