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

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.

Evaluation of Microvascular Density in Glioblastomas in Relation to p53 and Ki67 Immunoexpression

“…Diffuse gliomas, originating from glial stem or progenitor cells [ 1 , 2 ], represent the most frequent tumors of the central nervous system in adults [ 3 ]. Glioblastomas, known as astrocytic glioma, grade 4, according to the WHO CNS classification [ 4 ], represent the most aggressive and lethal form of primary intracranial malignant tumor in adults [ 5 ]. The incidence rate of glioblastomas is 3.19–4.17/100,000 person-years [ 6 ], accounting for 50.1% of all malignant tumors of the central nervous system in the USA [ 7 ].…”