Introduction: In brain tumours, biopsy is often used to identify tumour-specific abnormalities so that treatments can be appropriately tailored. 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. We developed a method by which serial biopsy can be used to validate response to treatment in vivo using a mouse model of glioblastoma.
Aim: To determine whether it is possible to conduct serial brain biopsies in mouse models causing minimal morbidity and if so whether the technique may facilitate evaluation of tumour response to chemotherapy.
Methods: Twenty immunodeficient mice underwent stereotactic cortical implants with the human glioma cell line U87MG, modified to express active EGFR (EGFRvIII), green fluorescent protein and luciferase. Tumour growth was monitored using bioluminescence imaging. Once tumours reached a mimimum size (>107 photons per second), one group (n=10) underwent free hand biopsy under anaesthesia. During the recovery period the biopsy group and control group (n= 10) were monitored using a neurological severity score (NSS). After recovery, PF-00299804 was administered. The biopsy group underwent a second biopsy two hours after treatment. All mice were then allowed to recover and were euthanised upon tumour-related morbidity.
Results: All mice survived the surgical procedures with minimal perioperative morbidity and recovered to similar levels as controls over a period of five days. Serial tissue samples were successfully obtained and were of sufficient quality to assess drug-target inhibition using immunohistochemistry.
Conclusion: We have shown it is possible to conduct serial biopsies in brain tumour bearing mice to obtain viable tissues samples that may be used to assess response to treatment in other types of tumour model.