Glioma: From Intracellular Oncogenic Pathways to Targeting Therapeutic Strategies

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 626

Special Issue Editor


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Guest Editor
Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA
Interests: glioblastoma; radiation resistance; chemotherapeutic resistance; extracellular vesicles; non-coding RNAs

Special Issue Information

Dear Colleagues,

Gliomas are the most common and aggressive type of primary brain tumors originating from glial cells. This review discusses the molecular mechanisms and intracellular oncogenic pathways driving glioma progression and highlights recent therapeutic advancements. Key oncogenic pathways such as PI3K/AKT/mTOR, MAPK/ERK, and Notch are critically involved in glioma growth, survival, invasion, and treatment resistance. Genetic and epigenetic modifications, including mutations in IDH1/2, EGFR amplification, and methylation of the MGMT promoter, play crucial roles in tumor behavior and patient prognosis. The challenges of developing effective treatments due to glioma’s highly heterogeneous nature and the presence of the blood–brain barrier. Traditional therapies like surgery, radiation, and chemotherapy (e.g., temozolomide) often face limitations due to resistance mechanisms and recurrence. Recent advances include molecularly targeted therapies, such as inhibitors of key pathways (e.g., EGFR inhibitors, PI3K/mTOR inhibitors), immunotherapy approaches (e.g., CAR T-cell therapy, immune checkpoint inhibitors), and novel drug delivery systems like nanocarriers to cross the BBB. Moreover, personalized medicine approaches and combination therapies are emphasized for their potential to enhance treatment efficacy and patient outcomes. Therefore, understanding the intricate molecular landscape of gliomas provides avenues for developing targeted therapeutic strategies aimed at overcoming the current limitations and improving patient prognosis.

This Special Issue aims to explore the complex biology and therapeutic challenges associated with gliomas, focusing on the molecular and cellular mechanisms underlying glioma initiation, progression, and resistance to treatment. It also provides a comprehensive understanding of intracellular oncogenic pathways that drive glioma development and highlights the translation of these findings into novel therapeutic strategies.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Insights into key signaling pathways and their roles in glioma progression and survival, along with genetic and epigenetic alterations that affect tumor biology and patient prognosis.
  • Advances in targeted therapies, immunotherapy strategies including CAR T-cells, vaccines, oncolytic viruses, immune checkpoint inhibitors, and novel drug delivery systems designed to cross the blood–brain barrier.
  • Mechanisms leading to treatment resistance and strategies to overcome them.
  • Understanding tumor heterogeneity and its impact on therapeutic response.
  • Development of personalized treatment regimens based on individual tumor profiles, supported by preclinical and clinical studies focusing on combination therapies and patient-tailored treatments.

Dr. Shilpi Singh
Guest Editor

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Keywords

  • glioma
  • targeted therapies
  • resistance mechanisms
  • oncogenic pathways
  • therapeutic resistance
  • combination therapies
  • tumor heterogeneity

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Published Papers (1 paper)

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Review

15 pages, 1316 KB  
Review
The Role of Pyk2 Kinase in Glioblastoma Progression and Therapeutic Targeting
by Lilia Kucheryavykh and Yuriy Kucheryavykh
Cancers 2025, 17(16), 2611; https://doi.org/10.3390/cancers17162611 - 9 Aug 2025
Viewed by 386
Abstract
Glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options and poor prognosis. Proline-rich tyrosine kinase 2 (Pyk2) has been implicated in regulation of GBM invasion, proliferation, and recurrence. Its activation, driven by tumor-infiltrating microglia and macrophage-derived extracellular factors such as [...] Read more.
Glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options and poor prognosis. Proline-rich tyrosine kinase 2 (Pyk2) has been implicated in regulation of GBM invasion, proliferation, and recurrence. Its activation, driven by tumor-infiltrating microglia and macrophage-derived extracellular factors such as EGF, PDGFB, SDF-1α, IL-6, and IL-8, enhances tumor cell motility and survival. Experimental studies demonstrate that pharmacological inhibition or genetic knockdown of Pyk2 significantly reduces glioma cell migration and proliferation. Furthermore, recurrent GBM tumors exhibit elevated Pyk2 phosphorylation in mouse GBM models, correlating with increased tumor growth. Inhibition of Pyk2 and the structurally related focal adhesion kinase (FAK) signaling has shown promising results in preclinical studies, reducing tumor recurrence and improving survival outcomes. This review summarizes recent findings and underscores the pivotal role of Pyk2 in GBM pathophysiology, highlighting its potential as a therapeutic target. Full article
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