Targeted Glioma Therapy—Clinical Trials and Future Directions

Abstract

Glioblastoma multiforme (GBM) is the most common type of glioma, with a median survival of 14.6 months post-diagnosis. Understanding the molecular profile of such tumors allowed the development of specific targeted therapies toward GBM, with a major role attributed to tyrosine kinase receptor inhibitors and immune checkpoint inhibitors. Targeted therapeutics are drugs that work by specific binding to GBM-specific or overexpressed markers on the tumor cellular surface and therefore contain a recognition moiety linked to a cytotoxic agent, which produces an antiproliferative effect. In this review, we have summarized the available information on the targeted therapeutics used in clinical trials of GBM and summarized current obstacles and advances in targeted therapy concerning specific targets present in GBM tumor cells, outlined efficacy endpoints for major classes of investigational drugs, and discussed promising strategies towards an increase in drug efficacy in GBM.

Peptide-Hitchhiking for the Development of Nanosystems in Glioblastoma

“…Numerous clinical trials (CTs) exploring different approaches to treating GBM are showing promise for potential therapies. − However, when it comes to strategies for functionalizing NPs with peptides, there are very few examples available. One promising advanced treatment option is 2B3–101, glutathione PEGylated liposomes that completed Phase I/IIa clinical trials for brain tumor therapy (NCT01386580).…”

New insights into targeted therapy of glioblastoma using smart nanoparticles

“…The most up-to-date WHO guidelines for classifying neoplastic masses of the CNS adopt markers of genetic and epigenetic nature. However, gliomas can also be categorized based on a grading system; namely low-grade gliomas (LGG) and high-grade gliomas (HGG) which correspond to WHO grades 1–2 and 3–4, respectively [ 3 ].…”

“…The prevailing glioma is GBM, essentially an astrocytoma of WHO grade 4, which represents 14.3% of primary CNS neoplasms, constituting 49.1% of all malignant brain tumors [ 2 , 3 ]. GBM as a strongly aggressive neoplasm of the CNS [ 5 , 6 ] correlated with very unfavorable patient prognosis [ 7 ] which the 5-year survival is roughly 7% [ 2 ].…”

“…In order to enhance our understanding of the molecular foundations of GBM, comprehensive analyses have been conducted [ 3 ]. In 2010, these analyses facilitated the categorization of glioblastomas into subtypes based on their transcriptional activity.…”

Insights into brain tumor diagnosis: exploring in situ hybridization techniques

“…It’s crucial to note the continued absence of effective therapeutic strategies for the most prevalent types of brain tumors ( 2 , 3 ). Early diagnosis and molecular-genetic profiling of tumors are emerging as promising avenues for developing treatment modalities ( 4 , 5 ).…”