Abstract
A breakthrough in drug discovery for glioblastoma requires serial collection of tissue from the central nervous system via window of opportunity trials
Therapeutic drug development in glioblastoma has remained static despite numerous clinical trials, advances in tumor biology, and substantial public interest. Since 2005, more than 1,250 interventional glioblastoma trials have been registered on ClinicalTrials.gov. Of these, 1,100 are phase 1 or 2 trials, most of which are dose-escalation studies. Unfortunately, these often provide little insight into whether drugs reach the tumor, exert a biological effect, or can overcome mechanisms of resistance. Trials often evaluate drugs that show promise in early development but subsequently fail at later stages. Biological understanding of these failures requires tissue samples before and after treatment, but the collection of these has not been a routine element of either neurosurgical practice or drug development in neuro-oncology. Window of opportunity (WoO) trials can help to determine the mechanisms of drug failure, but expanding their use requires a clearly defined nomenclature, serial access to tissue, and standardized design principles and outcomes. To achieve the clinical success seen for other malignancies, a culture change within the neurosurgical and neuro-oncology community is necessary to support repeated tissue collection from the central nervous system (CNS).