Autophagic and Apoptotic Pathways as Targets for Chemotherapy in Glioblastoma

• Published in: International journal of molecular sciences Vol. 19; no. 12; p. 3773
• Main Authors: Trejo-Solís, Cristina, Serrano-Garcia, Norma, Escamilla-Ramírez, Ángel, Castillo-Rodríguez, Rosa A, Jimenez-Farfan, Dolores, Palencia, Guadalupe, Calvillo, Minerva, Alvarez-Lemus, Mayra A, Flores-Nájera, Athenea, Cruz-Salgado, Arturo, Sotelo, Julio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27-11-2018; MDPI
• Subjects: Angiogenesis; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; autophagia; Autophagy; Autophagy - drug effects; Biomarkers; Brain cancer; Brain tumors; Cell cycle; Cell death; Cell growth; Cell proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Chemotherapy; Clinical Trials as Topic; Cytotoxicity; Drug Discovery; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastoma cells; Glioma; Glioma - drug therapy; Glioma - genetics; Glioma - metabolism; Glioma - pathology; Growth factors; High resistance; Humans; Kinases; Life expectancy; Life span; Ligands; Lymphoma; Mitochondria; Molecular Targeted Therapy; Phagocytosis; Proteins; Radiation therapy; Recruitment; Review; Signal Transduction - drug effects; signaling pathways; therapeutic targets; Treatment Outcome; Tumor necrosis factor-TNF; Tumors; apoptosis; autophagia; glioblastoma; signaling pathways; therapeutic targets; chemotherapy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19123773

Glioblastoma multiforme is the most malignant and aggressive type of brain tumor, with a mean life expectancy of less than 15 months. This is due in part to the high resistance to apoptosis and moderate resistant to autophagic cell death in glioblastoma cells, and to the poor therapeutic response to conventional therapies. Autophagic cell death represents an alternative mechanism to overcome the resistance of glioblastoma to pro-apoptosis-related therapies. Nevertheless, apoptosis induction plays a major conceptual role in several experimental studies to develop novel therapies against brain tumors. In this review, we outline the different components of the apoptotic and autophagic pathways and explore the mechanisms of resistance to these cell death pathways in glioblastoma cells. Finally, we discuss drugs with clinical and preclinical use that interfere with the mechanisms of survival, proliferation, angiogenesis, migration, invasion, and cell death of malignant cells, favoring the induction of apoptosis and autophagy, or the inhibition of the latter leading to cell death, as well as their therapeutic potential in glioma, and examine new perspectives in this promising research field.