25 MAR 2024

Brain cancer, particularly glioblastoma, stands as one of the most aggressive and lethal forms of cancer, primarily affecting the brain's glial cells. Glioblastoma is notorious for its rapid progression and resistance to current treatments, leading to a median survival of just over one year post-diagnosis^{1, 2}. For research seeking relevant models to develop therapeutics to combat such a daunting prognosis, Pharmacology Discovery Services (PDS) offers efficacy testing in human glioblastoma orthotopic models.

Glioblastoma symptoms can include headaches, seizures, cognitive deficits, and personality changes, significantly impairing quality of life³. Despite medical advancements, the treatment of glioblastoma—typically a combination of surgery, radiation, and chemotherapy—remains largely palliative, with recurrence almost inevitable4. The complexity of the brain's architecture and the blood-brain barrier further complicate effective treatment delivery, highlighting the critical need for more innovative therapeutic approaches.

In this context, the development of orthotopic brain cancer models, such as with U87 MG-Luciferized cell line, is pivotal. By introducing human glioblastoma cells directly into the brain of mice, this approach closely mimics the tumor's growth, microenvironment, and interaction with surrounding brain tissue in patients. This level of biological relevance is crucial for evaluating the efficacy and safety of potential new drugs in a context that closely resembles human disease.

Brain orthotopic models offer a sophisticated platform for deciphering the intricacies of tumor biology, testing the ability of therapeutic agents to cross the blood-brain barrier, and ultimately, developing more effective and targeted treatments for glioblastoma. The labeled cell line offers both in-life and ex vivo imaging for monitoring tumor progression and metastasis, as well as examination of drug (if labeled) and tumor cell interaction. Through this innovative approach, our aim is to pave the way for breakthroughs in glioblastoma therapy, offering hope for improved outcomes and quality of life for patients battling this formidable disease.

PDS offers efficacy testing in the U87 MG-Luc human glioblastoma orthotopic model. The animals, specific-pathogen-free (SPF) female nu/nu mice, will be orthotopically (intracranial) injected with U87 MG-Luc upon positioned in a stereotactic frame^{5, 6, 7}. Dose administrations (IV, IP, SC, or PO) are initiated one-week post-tumor cell implantation, upon assessing total flux (photos per second) with IVIS Spectrum for bioluminescent signal. IVIS Spectrum imaging is measured once to twice per week with biweekly body weight monitoring. The study period can be up to 4 weeks followed by tumor metastases analysis in vivo and ex vivo at the study endpoint. In addition to the tumor volume measurement, other optional services may be selected upon request to enable greater prediction of success in the clinic, including (but not limited to) MTD determination, clinical chemistry, CBC, PK analysis, histopathology, and biomarker analysis.

Our laboratory staff has an average of 15 years of experience in conducting in vivo pharmacology studies. Relative husbandry and animal handling comply with the species-specific recommendations of the Guide for the Care and Use of Laboratory Animals (2011), a respected scientific resource compiled by a committee of recognized experts. And they are conducted within the facility accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC), an international nonprofit that promotes humane treatment of animals in science.

Figure 1. A. NU/NU and SCID mice were inoculated with 1x10⁵ or 5x10⁴ U87-MG-Luc cells/mouse intracranially into the brain. Tumor growth was measured by bioluminescence signal with IVIS Spectrum. B. NU/NU mice were inoculated with 5x10⁴ U87-MG-Luc cells/mouse intracranially into the brain. Treatment was initiated 7 days post tumor implantation and denoted as Day 1.

(*) indicates a significant (p < 0.05) reduction in tumor size compared to vehicle control as measured by bioluminescence signal with IVIS Spectrum.

Resources

Brochure

In Vivo Oncology Models for Drug Discovery