Glioblastoma Targeted Therapy: Updated Approaches
Recent advances in biotechnology have resulted in updated approaches to glioblastoma-targeted therapy. These approaches aim to overcome current treatments’ limitations, including the inability to cross the blood-brain barrier and tumor intrinsic heterogeneity, contributing to treatment resistance. The recent development of immuno-mediated and biological therapies may overcome these challenges, and ongoing trials are expected to improve outcomes.
Barriers to Glioblastoma Targeted Therapy
The most common malignant brain tumor, glioblastoma (GBM), has a poor prognosis and a wide range of treatment options. Standard therapies include chemotherapy, radiation, and surgery. However, medical experts like the Glioblastoma Foundation professionals assert that developments in molecular pathology have made it possible to develop new and more potent treatments.
Targeting tumor cells expressing the insulin-like growth factor receptor can potentially extend the life of patients with this disease. New treatments are being developed to target the receptors on the brain’s surface. Specifically, these therapies target the EGF receptors, which regulate growth and survival in glioblastoma.
Advances in intraoperative imaging have helped surgeons better define tumor margins and enhance treatment precision. In addition, novel agents have been developed to disrupt the blood-brain barrier. However, many unanswered questions remain about the role of image-guided surgery.
Current studies show that CD8+ T cells infiltrating newly diagnosed patients can improve survival and outcomes. The CNS is a unique immune environment. It has a distinct phenotype characterized by distinct immune responses. In a healthy brain, immunologically quiescent cells, or microglia, make up 10% of CNS cells. Conversely, low levels of CD4+ T cells predict a poor prognosis in high-grade gliomas.
Clinical Trials Exploring Molecularly Matched Therapies
Molecularly matched therapies for glioblastoma are an important way to treat this aggressive cancer. These therapies can target specific molecular abnormalities in glioma cells, optimizing the treatment of high-risk patients. These therapies can also help improve long-term outcomes and minimize side effects.
While current therapies have shown promise, they are also associated with limitations. Some therapies failed to show results when patients were treated based on molecular biomarkers. The clinical trial for vemurafenib only included, For example, patients with GBM. Another limitation was that the trial was a single-arm study.
In 2016, the World Health Organization (WHO) incorporated molecular diagnostic methods into classifying gliomas. Molecular profiling is important because it provides valuable information about the tumor’s phenotype and prognosis.
The two drugs are not the same, but they have the same mechanism of action. Selinexor blocks a protein called CRM1, which may inhibit tumor growth and kill cancer cells. In contrast, temozolomide damages the cell’s DNA and is a powerful chemotherapy drug. Together, these two treatments may help shrink or stabilize brain tumors.
One treatment currently undergoing clinical trials is bevacizumab. This monoclonal antibody has shown promising results when combined with cetuximab in patients with advanced cancer.
Challenges of Drug Delivery Via Systemic Administration
Drug delivery via systemic administration is a key goal of GBM-targeted therapy, but it is also a major challenge. GBM tumors are typically highly heterogeneous and are not always readily accessible to systemically administered agents. In addition, the blood-brain barrier, which is made up of a complex network of glial and endothelial cells, limits the ability of most agents to penetrate the brain and reach the brain parenchyma.
One method of drug delivery is by catheter. This type of systemic administration allows for continuous drug delivery to the brain. Catheters are connected to a syringe/drug delivery pump and typically inserted into the tumor. In this method, a positive pressure gradient promotes the transport of drugs through a greater area than is possible with diffusion-limited delivery. This method allows for lower doses of drugs.
Another method of systemic drug delivery involves a peptide conjugated with a specific receptor. For example, in a mouse model, a peptide conjugated with an IL-4 or transferrin receptor could selectively target glioma cells and induce an anti-tumor response. However, this method has some limitations, including low in vivo stability and a short half-life. Moreover, these peptides may undergo degradation by proteolysis in the circulatory system, limiting their bioavailability. However, these drawbacks can be overcome by modifying the peptides or conjugating them with macromolecules or nanocarriers.
Despite these difficulties, organizations like the Glioblastoma Foundation support studies into local drug delivery, which is a fascinating substitute for GBM-targeted therapy. Several approaches have been explored, including films, foams, and gels. Hydrogels have gained much attention recently as they are injectable, biocompatible, and biodegradable. Moreover, gels can be engineered to control their release time.