Glioblastoma Treatment Modalities besides Surgery

Abstract

Glioblastoma multiforme (GBM) is commonly known as the most aggressive primary CNS tumor in adults. The mean survival of it is 14 to 15 months, following the standard therapy from surgery, chemotherapy, to radiotherapy. Efforts in recent decades have brought many novel therapies to light, however, with limitations. In this paper, authors reviewed current treatments for GBM besides surgery. In the past decades, only radiotherapy, temozolomide (TMZ), and tumor treating field (TTF) were approved by FDA. Though promising in preclinical experiments, therapeutic effects of other novel treatments including BNCT, anti-angiogenic therapy, immunotherapy, epigenetic therapy, oncolytic virus therapy, and gene therapy are still either uncertain or discouraging in clinical results. In this review, we went through current clinical trials, underlying causes, and future therapy designs to present neurosurgeons and researchers a sketch of this field.

Keywords: glioblastoma; novel treatment; therapy.

Figure 1

Temozolomide, lomustine, carmustine, and cyclophosphamide inhibit the tumor growth by alkylating/methylating DNAs and impeding DNA crosslinking

Figure 2

(A) TTF rupture tumor cell membrane by accumulating all polar molecules and dipoles in the cleavage furrow during the interdivision stage. (B) Boron-10 in tumor cells, radiated with thermal neutrons, releases high linear energy transfer (LET) α and 7Li particles. Both alpha particles and the lithium ions produce closely spaced ionizations in the immediate vicinity of the reaction, leading to a selective tumor cell killing.

Figure 3

(A) Bevacizumab prevents VEGF from binding its receptor on endothelial cells to reduce tumor angiogenesis and tumor growth. (B) Nimotuzumab binds to EGFR, blocking consequential downstream pathways to inhibit angiogenesie and GBM growth

Figure 4

Viral infection and replication lyse tumor cells. The release of tumor-associated antigens induce systemic anti-tumor immunity.

Figure 5

Gene therapy strategies. (A) Targeting the tumor microenvironment: viruses carry enzymes that degrade ECM components or anti-angiogenic factors that reduce vascular support of tumor. (B) GBM cells receive suicide genes from local injection of a carrier, together with systemic delivery of a prodrug. The suicide gene converts the prodrug into cytotoxic agents that kill the recipient cell and non-transduced bystander tumor cells. (C) The gene for an immunomodulatory cytokine is delivered to the tumor cells by viruses. Cytokine expression increases tumor cell apoptosis and activates immune cells such as macrophages, natural killer cells, and T-cell lymphocytes. (D) Tumor cells receive the functional copy of a tumor suppressor gene, which subsequently induces apoptosis.