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. 2024 May 24;14(6):673.
doi: 10.3390/life14060673.

Overcoming Resistance to Temozolomide in Glioblastoma: A Scoping Review of Preclinical and Clinical Data

Dimitra Smerdi  1 , Myrto Moutafi  1 , Ioannis Kotsantis  1 , Lampis C Stavrinou  2 , Amanda Psyrri  1
Affiliations

Overcoming Resistance to Temozolomide in Glioblastoma: A Scoping Review of Preclinical and Clinical Data

Dimitra Smerdi et al. Life (Basel). .

Abstract

Glioblastoma (GB) is the most common and most aggressive primary brain tumor in adults, with an overall survival almost 14.6 months. Optimal resection followed by combined temozolomide chemotherapy and radiotherapy, also known as Stupp protocol, remains the standard of treatment; nevertheless, resistance to temozolomide, which can be obtained throughout many molecular pathways, is still an unsurpassed obstacle. Several factors influence the efficacy of temozolomide, including the involvement of other DNA repair systems, aberrant signaling pathways, autophagy, epigenetic modifications, microRNAs, and extracellular vesicle production. The blood-brain barrier, which serves as both a physical and biochemical obstacle, the tumor microenvironment's pro-cancerogenic and immunosuppressive nature, and tumor-specific characteristics such as volume and antigen expression, are the subject of ongoing investigation. In this review, preclinical and clinical data about temozolomide resistance acquisition and possible ways to overcome chemoresistance, or to treat gliomas without restoration of chemosensitinity, are evaluated and presented. The objective is to offer a thorough examination of the clinically significant molecular mechanisms and their intricate interrelationships, with the aim of enhancing understanding to combat resistance to TMZ more effectively.

Keywords: chemoresistance; glioblastomas; resistance mechanisms; temozolomide resistance; therapeutic agents.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Chemical structure of temozolomide and mechanism of action (MTIC: monomethyl 5-triazino imidazole carboxamide).
Figure 2
Figure 2
Tumor microenvironment. (ECM: extracellular matrix).
Figure 3
Figure 3
Main preclinical and clinical data on overcoming resistance to temozolomide in GB.
See this image and copyright information in PMC

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