[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-373384-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-373384-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","signaling-pathways-in-gliomas","Signaling Pathways in Gliomas","","Changes in cell signaling pathways that maintain normal cell homeostasis can trigger transformation into cancer cells. Altered metabolism is highlighted as a cancer hallmark, making it crucial to understand enzymes regulating metabolism and respiration and the intracellular pathways they connect to. Such pathway rewiring can provide prognostic and predictive value, particularly for molecularly targeted therapies. Gliomas, the most common primary malignant brain tumors, depend strongly on growth and angiogenesis pathway aberrations, including PI3K/Akt and RAS/MAPK/ERK signaling, and dysregulated hexokinases (e.g., HK2) driving glycolysis, autophagy, and apoptosis, while heterogeneity and immunosuppression cause therapeutic 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Claudia Ricci and Yutaka Suzuki  \nReceived: 30 March 2025  \nRevised: 10 May 2025  \nAccepted: 16 May 2025  \nPublished: 19 May 2025  \nCitation: Stachyra, P.; Grzybowska-Szatkowska, L. Signaling Pathways in Gliomas. Genes 2025, 16, 600. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)genes16050600  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 II Department of Oncology and Clinical Immunology with Day Chemotherapy, Oncology Centre of the Lublin Region, Jaczewskiego 7, 20-090 Lublin, Poland  \n2 Department of Radiotherapy, Medical University of Lublin, Chod´zki 7, 20-093 Lublin, Poland; [ludmila.grzybowska-szatkowska@umlub.pl](ludmila.grzybowska-szatkowska@umlub.pl)  \n* [Correspondence: paulina.stachyra@gmail.com](Correspondence: paulina.stachyra@gmail.com)  \nAbstract: Changes in cell signaling pathways, which in normal conditions determine the maintenance of cell homeostasis and the correctness of its basic processes, may cause the transformation of a normal cell into a cancer cell. Alterations in cellular metabolism leading to oncogenesis are considered to be a hallmark of cancer cells. Therefore, a thorough understanding of cellular enzymes affecting metabolism and respiration, as well as intracellular pathways connected with them, seems crucial. These changes may be both prognostic and predictive factors, especially in terms of using molecularly targeted therapies. Aberrationsin the pathways responsible for cell growth and angiogenesis are considered particularly important in the process of oncogenesis. Gliomas are the most common primary malignant tumors of the brain. The most important molecular disorders determining their particularly malignant nature are aberrations in the pathways responsible for cell growth and angiogenesis, such as the PI3K/Akt or RAS/MAPK/ERK signaling pathway, as well as excessive activity of enzymes, like hexokinases, which play a key role in glycolysis, autophagy, and apoptosis. The multitude of alterations detected in glioma cells, high heterogeneity, and the immunosuppressive environment within the tumor are the main features causing failuresin the attempts to implement modern therapies.  \nKeywords: glioma; cellular pathways; RAS/MAPK/ERK; PI3K/Akt; MGMT; IDH; HK2  \n1. Introduction  \nGliomas are the most common primary malignant tumors of the brain [1] . Among adults, the most common tumors are those derived from astrocytes [2] . The global incidence of stellate tumors is 2.98/100,000 and increases rapidly in patients over 40 years of age [2] . The most prevalent cancer in this group is WHO G4 glioblastoma multiforme (GBM), characterized by high malignancy and short overall survival of 13.5 months. The use of radiotherapy and temozolamide in the treatment slightly prolongs the average survival time (15.6 months) . The 5-year survival rate is only about 5%[3] . The etiology of brain gliomas remains uncertain, and their pathogenesis is highly complex. Co-occurring alterations in many signaling pathways in charge of cell proliferation, differentiation, and apoptosis, as well as numerous mutations of genes encoding enzymes, are probably responsible [4] .  \nThe only modifiable factor that undoubtedly causes an increased risk of developing glioblastoma multiforme is ionizing radiation. Gliomas are more often detected in people who underwent high-dose radiotherapy to the head and neck area in childhood [5], in people suffering from genetic syndromes such as Li-Fraumeni syndrome or Lynch syndrome [6], or in people who have had low-grade glioma in the past [7] . It i","cbCaiu3EmPvnZmdw","https://ap.wps.com/l/cbCaiu3EmPvnZmdw","pdf",1710531,22,"English","# Abstract\n# Keywords\n# 1. Introduction\n# Table 1. Division of selected glioma types by malignancy degree (5th WHO CNS classification)\n# Table 2. Glioma groups and features by IDH mutation status","[{\"question\":\"Why are signaling pathway changes important in gliomas?\",\"answer\":\"Alterations in signaling pathways can shift a normal cell toward cancer by disrupting core processes that maintain homeostasis, including pathways controlling cell growth and angiogenesis.\"},{\"question\":\"Which metabolic and signaling mechanisms are emphasized as key glioma drivers?\",\"answer\":\"The article highlights pathway aberrations such as PI3K/Akt and RAS/MAPK/ERK, along with excessive enzyme activity like hexokinases (e.g., HK2) that influence glycolysis, autophagy, and apoptosis.\"},{\"question\":\"What factors contribute to failures of modern glioma therapies?\",\"answer\":\"High heterogeneity in glioma cells and the immunosuppressive tumor environment are identified as main reasons attempts to implement modern therapies can fail.\"}]","Signaling Pathways in Gliomas | PDF",1790199455,55]