Abstract
Glioblastoma multiforme (GBM) is a type of brain tumor that is notorious for its aggressiveness and invasiveness, and the complete removal of GBM is still not possible, even with advanced diagnostic strategies and extensive therapeutic plans. Its dismal prognosis and short survival time after diagnosis make it a crucial public health issue. Understanding the molecular mechanisms underlying GBM may inspire novel and effective treatments against this type of cancer. At a molecular level, almost all tumor cells exhibit telomerase activity (TA), which is a major means by which they achieve immortalization. Further studies show that promoter mutations are associated with increased TA and stable telomere length. Moreover, some tumors and immortalized cells maintain their telomeres with a telomerase-independent mechanism termed the “alternative lengthening of telomeres” (ALT), which relates to the mutations of the α-thalassemia/mental retardation syndrome X-linked protein (ATRX), the death-domain associated protein (DAXX) and H3.3. By means of the mutations of the telomerase reverse transcriptase (TERT) promoter and ATRX/DAXX, cancers can immortalize and escape cell senescence and apoptosis. In this article, we review the evidence for triggering GBM cell death by targeting telomerase and the ALT pathway, with an extra focus on a plant-derived compound, butylidene phthalide (BP), which may be a promising novel anticancer compound with good potential for clinical applications.
Highlights
Despite their low incidence rate (25.48 per 100,000 person-years) [1], brain tumors are one of the most frightening diseases, because of their high morbidity and mortality rate and because of the heavy burden they place on patients, their loved ones, and healthcare systems
The results indicate that the polygenic, instead of the monogenic, model, may explain the incidence pattern of adult gliomas, and results from genome-wide association studies have supported this conclusion by identifying variations in eight genomic regions as contributing to the risk of developing gliomas: telomerase RNA component (TERC), telomerase reverse transcriptase (TERT), epidermal growth factor receptor (EGFR), coiled-coil domain containing 26,cyclin-dependent kinase inhibitor 2B, pleckstrin homology such as domain family B member 1, tumor protein p53 (TP53), and the regulator of telomere elongation helicase 1 (RTEL1) [37,38,39,40,41]
These findings suggest that chromosomes 1p and 19q may contain tumor suppressor genes, including the far upstream element binding protein 1 (FUBP1) on chromosome 1p and the capicua transcriptional repressor (CIC) on chromosome 19q [59,60,61]
Summary
Despite their low incidence rate (25.48 per 100,000 person-years) [1], brain tumors are one of the most frightening diseases, because of their high morbidity and mortality rate and because of the heavy burden they place on patients, their loved ones, and healthcare systems. Since treatment decisions and prognoses are based on histological diagnoses and grading, the latest version of the World Health Organization CNS tumors classification has undergone a complete transformation by incorporating molecular criteria in addition to the pre-existing histological parameters to minimize subjective interpretation of morphological descriptions, as well as interobserver variation, and to provide more objective, quantitative, and reproducible results for recording the grade and lineage of gliomas [5]. The diffuse, invasive nature and location of brain tumors suggest that it is barely possible for an effective treatment to destroy all tumor cells This reality underscores the need for continuing investigations of novel and alternative therapeutic options, including clinical trials of any agents showing therapeutic potential
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
