Related Experiment Video
Updated: Jul 10, 2026
Longitudinal Intravital Imaging of Brain Tumor Cell Behavior in Response to an Invasive Surgical Biopsy
Published on: May 3, 2019
A novel technique of serial biopsy in mouse brain tumour models
Sasha Rogers1,2,3, Hilary Hii1,2, Joel Huang1
1Telethon Kids Institute, Perth, WA, Australia.
Abstract:
Biopsy is often used to investigate brain tumour-specific abnormalities so that treatments can be appropriately tailored. Dacomitinib (PF-00299804) is a tyrosine kinase inhibitor (TKI), which is predicted to only be effective in cancers where the targets of this drug (EGFR, ERBB2, ERBB4) are abnormally active. Here we describe a method by which serial biopsy can be used to validate response to dacomitinib treatment in vivo using a mouse glioblastoma model. In order to determine the feasibility of conducting serial brain biopsies in mouse models with minimal morbidity, and if successful, investigate whether this can facilitate evaluation of chemotherapeutic response, an orthotopic model of glioblastoma was used. Immunodeficient mice received cortical implants of the human glioblastoma cell line, U87MG, modified to express the constitutively-active EGFR mutant, EGFRvIII, GFP and luciferase. Tumour growth was monitored using bioluminescence imaging. Upon attainment of a moderate tumour size, free-hand biopsy was performed on a subgroup of animals. Animal monitoring using a neurological severity score (NSS) showed that all mice survived the procedure with minimal perioperative morbidity and recovered to similar levels as controls over a period of five days. The technique was used to evaluate dacomitinib-mediated inhibition of EGFRvIII two hours after drug administration. We show that serial tissue samples can be obtained, that the samples retain histological features of the tumour, and are of sufficient quality to determine response to treatment. This approach represents a significant advance in murine brain surgery that may be applicable to other brain tumour models. Importantly, the methodology has the potential to accelerate the preclinical in vivo drug screening process.
Insights
Serial biopsy in a mouse glioblastoma model allows for in vivo validation of targeted therapies like dacomitinib. This minimally invasive technique enables precise assessment of drug response, accelerating preclinical research for brain tumors.
Area of Science:
- Neuro-oncology
- Surgical Innovation
- Pharmacodynamics
Background:
- Brain tumor biopsies are crucial for tailoring treatments.
- Dacomitinib, a tyrosine kinase inhibitor (TKI), targets EGFR, ERBB2, and ERBB4, showing efficacy in cancers with aberrant activity of these targets.
- Preclinical models are essential for evaluating novel therapeutic strategies.
Purpose of the Study:
- To establish and validate a serial brain biopsy technique in a mouse glioblastoma model.
- To assess the feasibility and minimal morbidity of serial biopsies in vivo.
- To evaluate the utility of serial biopsies in determining response to dacomitinib treatment.
Main Methods:
- An orthotopic glioblastoma model was established using U87MG cells expressing EGFRvIII, GFP, and luciferase in immunodeficient mice.
- Tumor growth was monitored via bioluminescence imaging.
- Free-hand serial biopsies were performed, and animal well-being was assessed using a neurological severity score (NSS).
Main Results:
- Serial brain biopsies were successfully performed with minimal morbidity and rapid recovery in mice.
- The biopsy samples retained histological integrity and were suitable for analysis.
- The technique allowed for the evaluation of dacomitinib-mediated inhibition of EGFRvIII.
Conclusions:
- Serial brain biopsy is a feasible and valuable technique for preclinical assessment of targeted therapies in glioblastoma models.
- This methodology can accelerate the drug screening process by enabling in vivo validation of treatment response.
- The approach holds promise for application in other brain tumor models, advancing neuro-oncology research.
