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Review
. 2022 May 11;23(10):5351.
doi: 10.3390/ijms23105351.

Therapeutic Options in Neuro-Oncology

Mariana Afonso  1 , Maria Alexandra Brito  1   2
Affiliations
Review

Therapeutic Options in Neuro-Oncology

Mariana Afonso et al. Int J Mol Sci. .

Abstract

One of the biggest challenges in neuro-oncology is understanding the complexity of central nervous system tumors, such as gliomas, in order to develop suitable therapeutics. Conventional therapies in malignant gliomas reconcile surgery and radiotherapy with the use of chemotherapeutic options such as temozolomide, chloroethyl nitrosoureas and the combination therapy of procarbazine, lomustine and vincristine. With the unraveling of deregulated cancer cell signaling pathways, targeted therapies have been developed. The most affected signaling pathways in glioma cells involve tyrosine kinase receptors and their downstream pathways, such as the phosphatidylinositol 3-kinases (PI3K/AKT/mTOR) and mitogen-activated protein kinase pathways (MAPK). MAPK pathway inhibitors include farnesyl transferase inhibitors, Ras kinase inhibitors and mitogen-activated protein extracellular regulated kinase (MEK) inhibitors, while PI3K/AKT/mTOR pathway inhibitors are divided into pan-inhibitors, PI3K/mTOR dual inhibitors and AKT inhibitors. The relevance of the immune system in carcinogenesis has led to the development of immunotherapy, through vaccination, blocking of immune checkpoints, oncolytic viruses, and adoptive immunotherapy using chimeric antigen receptor T cells. In this article we provide a comprehensive review of the signaling pathways underlying malignant transformation, the therapies currently used in the treatment of malignant gliomas and further explore therapies under development, including several ongoing clinical trials.

Keywords: chloroethyl nitrosoureas; immunotherapy; malignant gliomas; signaling pathway inhibitors; temozolomide; tyrosine kinase receptor inhibitors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Carcinogenesis in brain cells. Figure drawn with smart.servier.com.
Figure 2
Figure 2
Malignant glioma signaling pathways. Figure drawn with smart.servier.com.
Figure 3
Figure 3
Temozolomide metabolism, mechanism of action and drug resistance. Atom color code: blue, nitrogen; grey, carbon; red, oxygen; white, hydrogen. Figure drawn with smart.servier.com and using molecules from PubChem [68,69,70,71,72].
Figure 4
Figure 4
Chloroethyl nitrosoureas metabolism, mechanism of action and drug resistance. Atom color codes: blue, nitrogen; grey, carbon; red, oxygen; white, hydrogen; green, chlorine; grey + white, radical. Figure drawn with smart.servier.com and using molecules from PubChem [78,79,80].
Figure 5
Figure 5
Targeted therapies for malignant glioma. Simplified representation of (A) tyrosine kinase receptor inhibitors, (B) IDH, gene fusion and MCT inhibitors and (C) specific inhibitors of intracellular downstream pathways. Figure drawn with smart.servier.com.
Figure 6
Figure 6
Vaccine therapy. Figure drawn with smart.servier.com.
Figure 7
Figure 7
Immune checkpoint blockade. Figure drawn with smart.servier.com.
Figure 8
Figure 8
Oncolytic viral therapy. Figure drawn with smart.servier.com.
Figure 9
Figure 9
CAR-T cell therapy. Figure drawn with smart.servier.com.
See this image and copyright information in PMC

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