Related Experiment Video
Updated: Sep 23, 2025
Establishment of Orthotopic Patient-derived Xenograft Models for Brain Tumors using a Stereotaxic Device
Published on: May 2, 2025
Leveraging the neurosurgical operating room for therapeutic development in NeuroOncology
Stephen R Lowe1, Katherine Kunigelis1, Michael A Vogelbaum1
1Department of NeuroOncology, Moffitt Cancer Center, Tampa, FL 33612, United States.
Abstract:
Glioblastoma (GBM) remains a disease with a dismal prognosis. For all the hope and promise immunotherapies and molecular targeted therapies have shown for systemic malignancies, these treatments have failed to show any promise in GBM. In this context, the paradigm of investigation of therapeutics for this disease itself must be examined and modifications considered. The unique challenge of the presence of blood-brain and blood-tumor barriers (BBB/BTB) raises questions about both the true levels of systemic drug delivery to the affected tissues. Window-of-opportunity (WoO) trials in neuro-oncology allow for proof-of-concept at the start of a classic phase I-II-III clinical trial progression. For therapeutics that do not have the ability to cross the BBB/BTB, direct delivery into tumor and/or tumor-infiltrated brain in the setting of a surgical procedure can provide a novel route of therapeutic access. These approaches permit neurosurgeons to play a greater role in therapeutic development for brain tumors.
Insights
Glioblastoma treatment faces challenges due to the blood-brain barrier. Direct drug delivery during surgery offers a promising new approach for brain tumor therapeutics.
Area of Science:
- Neuro-oncology
- Neurosurgery
- Pharmacology
Background:
- Glioblastoma (GBM) has a poor prognosis, with limited success for systemic immunotherapies and targeted therapies.
- The blood-brain and blood-tumor barriers (BBB/BTB) significantly impede effective drug delivery to brain tumors.
- Current therapeutic investigation paradigms for GBM require re-evaluation.
Purpose of the Study:
- To examine the challenges in glioblastoma (GBM) therapeutic development.
- To explore novel strategies for overcoming the blood-brain and blood-tumor barriers (BBB/BTB) in GBM treatment.
- To highlight the potential role of neurosurgery in delivering therapeutics directly to brain tumors.
Main Methods:
- Review of current therapeutic strategies and challenges in glioblastoma (GBM) treatment.
- Discussion of the impact of blood-brain and blood-tumor barriers (BBB/BTB) on systemic drug delivery.
- Exploration of direct intra-tumoral drug delivery methods during surgical procedures.
- Consideration of window-of-opportunity (WoO) trials in neuro-oncology.
Main Results:
- Systemic therapies have largely failed to demonstrate efficacy in glioblastoma (GBM).
- The blood-brain and blood-tumor barriers (BBB/BTB) present a critical obstacle for conventional drug delivery.
- Direct delivery of therapeutics during surgery bypasses the BBB/BTB, enabling higher local drug concentrations.
- Window-of-opportunity (WoO) trials can facilitate early proof-of-concept for novel neuro-oncology treatments.
Conclusions:
- Rethinking therapeutic investigation strategies is crucial for glioblastoma (GBM).
- Direct drug delivery via neurosurgical intervention offers a viable alternative to overcome the BBB/BTB.
- Neurosurgery can play an expanded role in the development and administration of brain tumor therapeutics.
More Related Videos
12:25Optimization of High Grade Glioma Cell Culture from Surgical Specimens for Use in Clinically Relevant Animal Models and 3D Immunochemistry
Published on: January 7, 2014
08:23Implementation of Minimally Invasive Brain Tumor Resection in Rodents for High Viability Tissue Collection
Published on: May 9, 2022
