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Molecular Insights into Glioblastoma Pathogenesis and Therapeutics
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Molecular Insights into Glioblastoma Pathogenesis and Therapeutics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 1230

Special Issue Editors

Dr. Claudia Desiderio

E-Mail Website
Guest Editor
Consiglio Nazionale delle Ricerche - Istituto di Scienze e Tecnologie Chimiche (SCITEC) "Giulio Natta", 00168 Rome, Italy
Interests: proteomics; peptidomics; post-translational modifications; cancer; biomarker; mass spectrometry
Special Issues, Collections and Topics in MDPI journals
Dr. Giovanni Sabatino

E-Mail Website
Guest Editor
Institute of Neurosurgery, IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Catholic University, Rome, Italy
Interests: glioma; neurosurgery; neuro-oncology; intraoperative fluorescence; radiomics; microRNAs
Dr. Edoardo Mazzucchi

E-Mail Website
Guest Editor
IRCCS Regina Elena National Cancer Institute, Rome, Italy
Interests: intraoperative imaging; tractography; awake craniotomy; neuro-oncology; brain connectivity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glioblastoma multiforme (GBM) is one of the most common brain tumors that can develop from low-grade astrocytic tumors or arise de novo. Despite aggressive multimodal therapy consisting of cytoreductive surgery, radiation therapy, and chemotherapy, the prognosis is extremely poor. Tumors that appear to be circumscribed and very focal according to standard neuroimaging data may nevertheless have tumor cells that infiltrate surrounding parenchyma around the edge, even far from the epicenter of the lesion. After surgical removal, more than 90% of GBM recur within the margins of the resection cavity or develop enhancing lesions at some distance from the original tumor, either in the ipsilateral or opposite hemisphere. Knowledge of the stem cells involved in glioblastoma tumorigenesis is of fundamental importance to understanding how this tumor arises and spreads and to the study new molecular targets. Although molecular features are now fundamental for the diagnosis, treatment, and prognostic classification of glioblastoma, this tumor is still far from being fully understood in its molecular basis, infiltration capacity, and resistance to treatments, and its molecular characterization is therefore strongly required to significantly improve prognosis, early intervention on recurrence, and targeted therapy.

In this Special Issue, we will discuss the progress in the knowledge of the molecular features of the brain tumor glioblastoma with a special focus on the elucidation of the mechanisms of disease onset and progression for the potential development of new therapeutic and treatment approaches in the perspective of clinical applications and diagnostic tool discovery increasingly oriented towards personalized medicine. From this standpoint, the integration of different and complementary skills, such as biochemistry and omics sciences, oncology, neurosurgery, and pathology, contributes to achieving a deeper understanding and promising results in a multidisciplinary approach to investigating the disease.

Dr. Claudia Desiderio
Dr. Giovanni Sabatino
Dr. Edoardo Mazzucchi
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • glioblastoma
  • proteomics
  • immunopeptidomics
  • genomics
  • extracellular vesicles
  • biomarkers
  • molecular mechanisms
  • i-knife mass spectrometry
  • intra-operative imaging
  • cancer stem cells
  • cancer progression
  • neurosurgery
  • radiomics
  • personalized medicine

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Published Papers (2 papers)

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Research

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29 pages, 2210 KiB  
Article
Proteomic Analysis of the Low Molecular Mass Fraction of Newly Diagnosed and Recurrent Glioblastoma CUSA Fluid: A Pilot Investigation of the Peptidomic Profile
by Alexandra Muntiu, Federica Vincenzoni, Diana Valeria Rossetti, Andrea Urbani, Giuseppe La Rocca, Alessio Albanese, Edoardo Mazzucchi, Alessandro Olivi, Giovanni Sabatino and Claudia Desiderio
Int. J. Mol. Sci. 2025, 26(13), 6055; https://doi.org/10.3390/ijms26136055 - 24 Jun 2025
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Abstract
Glioblastoma multiforme (GBM) is a highly aggressive, treatment-resistant grade IV brain tumor with poor prognosis that grows rapidly and invades surrounding tissues, complicating surgery and frequently recurring. Although the crucial role of endogenous peptides has been highlighted for several tumors, the specific peptidomic [...] Read more.
Glioblastoma multiforme (GBM) is a highly aggressive, treatment-resistant grade IV brain tumor with poor prognosis that grows rapidly and invades surrounding tissues, complicating surgery and frequently recurring. Although the crucial role of endogenous peptides has been highlighted for several tumors, the specific peptidomic profile of GBM remains unexplored to date. This study aimed to perform a preliminary characterization of the low molecular mass proteome fraction of Cavitron Ultrasonic Surgical Aspirator (CUSA) fluid collected from different tumor zones, i.e., the core and tumor periphery of newly diagnosed (ND) and recurrent (R) GBM. The samples, pooled by tumor type and collection zone, were centrifuged through molecular cut-off filter devices to collect the non-retained fraction of the proteome <10 kDa for direct full-length LC-MS analysis. A total of 40 and 24 peptides, fragments of 32 and 18 proteins, were marked as ND and R GBM COREs, respectively, while 132 peptides, fragments of 46 precursor proteins, were identified as common and included proteins which were cancer-related or involved in GBM pathophysiology. Besides providing a preliminary overview of the unexplored peptidome of GBM, this pilot study confirms peptidomics as a promising tool to discover potential GBM biomarkers in the perspective of clinical applications increasingly oriented towards a precision medicine approach. Data are available via ProteomeXchange with the identifier PXD060807. Full article
(This article belongs to the Special Issue Molecular Insights into Glioblastoma Pathogenesis and Therapeutics)
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Review

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50 pages, 937 KiB  
Review
Precision Neuro-Oncology in Glioblastoma: AI-Guided CRISPR Editing and Real-Time Multi-Omics for Genomic Brain Surgery
by Matei Șerban, Corneliu Toader and Răzvan-Adrian Covache-Busuioc
Int. J. Mol. Sci. 2025, 26(15), 7364; https://doi.org/10.3390/ijms26157364 - 30 Jul 2025
Viewed by 632
Abstract
Precision neurosurgery is rapidly evolving as a medical specialty by merging genomic medicine, multi-omics technologies, and artificial intelligence (AI) technology, while at the same time, society is shifting away from the traditional, anatomic model of care to consider a more precise, molecular model [...] Read more.
Precision neurosurgery is rapidly evolving as a medical specialty by merging genomic medicine, multi-omics technologies, and artificial intelligence (AI) technology, while at the same time, society is shifting away from the traditional, anatomic model of care to consider a more precise, molecular model of care. The general purpose of this review is to contemporaneously reflect on how these advances will impact neurosurgical care by providing us with more precise diagnostic and treatment pathways. We hope to provide a relevant review of the recent advances in genomics and multi-omics in the context of clinical practice and highlight their transformational opportunities in the existing models of care, where improved molecular insights can support improvements in clinical care. More specifically, we will highlight how genomic profiling, CRISPR-Cas9, and multi-omics platforms (genomics, transcriptomics, proteomics, and metabolomics) are increasing our understanding of central nervous system (CNS) disorders. Achievements obtained with transformational technologies such as single-cell RNA sequencing and intraoperative mass spectrometry are exemplary of the molecular diagnostic possibilities in real-time molecular diagnostics to enable a more directed approach in surgical options. We will also explore how identifying specific biomarkers (e.g., IDH mutations and MGMT promoter methylation) became a tipping point in the care of glioblastoma and allowed for the establishment of a new taxonomy of tumors that became applicable for surgeons, where a change in practice enjoined a different surgical resection approach and subsequently stratified the adjuvant therapies undertaken after surgery. Furthermore, we reflect on how the novel genomic characterization of mutations like DEPDC5 and SCN1A transformed the pre-surgery selection of surgical candidates for refractory epilepsy when conventional imaging did not define an epileptogenic zone, thus reducing resective surgery occurring in clinical practice. While we are atop the crest of an exciting wave of advances, we recognize that we also must be diligent about the challenges we must navigate to implement genomic medicine in neurosurgery—including ethical and technical challenges that could arise when genomic mutation-based therapies require the concurrent application of multi-omics data collection to be realized in practice for the benefit of patients, as well as the constraints from the blood–brain barrier. The primary challenges also relate to the possible gene privacy implications around genomic medicine and equitable access to technology-based alternative practice disrupting interventions. We hope the contribution from this review will not just be situational consolidation and integration of knowledge but also a stimulus for new lines of research and clinical practice. We also hope to stimulate mindful discussions about future possibilities for conscientious and sustainable progress in our evolution toward a genomic model of precision neurosurgery. In the spirit of providing a critical perspective, we hope that we are also adding to the larger opportunity to embed molecular precision into neuroscience care, striving to promote better practice and better outcomes for patients in a global sense. Full article
(This article belongs to the Special Issue Molecular Insights into Glioblastoma Pathogenesis and Therapeutics)
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