Findings, Insights and Perspectives on Central Nervous System Tumors

Topic Information

Dear Colleagues,

Central nervous system (CNS) cancers are neoplastic diseases stemming from the brain and its surrounding structures, with increasing incidence, and high mortality and morbidity rates worldwide. They are characterized by their aggressive nature, marked heterogeneity and adaptation to chemoresistance, leading to a poor prognosis and clinical outcome. With the ongoing advances in research, the medical field is trying to abandon the “one size fits all” philosophy and adopt a personalized medicine approach, developing novel drug and formulation strategies that can target specific disease biomarkers. The aim of this topic is to provide a forum for researchers and clinicians to share their latest findings, insights, and perspectives on CNS tumors. We welcome original research and review articles on a range of topics related to CNS neoplasms, including, but not limited to, the following: (1) the molecular and cellular mechanisms of cancer initiation, progression, and resistance; (2) advances in diagnosis and treatment; (3) novel drug delivery strategies for cancer therapy; (4) new diagnostic and prognostic biomarkers; (5) innovative 3D microphysiological models for cancer and tumor microenvironment research; and (6) the synergy of machine learning in designing more efficient therapies.

Dr. João Basso
Dr. Carla Vitorino
Dr. Rui Vitorino
Dr. Ana Fortuna
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Cancers cancers	4.5	8.0	2009	17.4 Days	CHF 2900
Cells cells	5.1	9.9	2012	17 Days	CHF 2700
Diseases diseases	2.9	0.8	2013	21.4 Days	CHF 1800
Nanomaterials nanomaterials	4.4	8.5	2010	14.1 Days	CHF 2400
Pharmaceutics pharmaceutics	4.9	7.9	2009	15.5 Days	CHF 2900

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Published Papers (5 papers)

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All Cancers Cells Diseases Nanomaterials Pharmaceutics

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Open AccessArticle

Cadherin Expression Profiles Define Glioblastoma Differentiation and Patient Prognosis

by Carolina Noronha, Ana Sofia Ribeiro, Rita Carvalho, Nuno Mendes, Joaquim Reis, Claudia C. Faria, Ricardo Taipa and Joana Paredes

Cancers 2024, 16(13), 2298; https://doi.org/10.3390/cancers16132298 - 22 Jun 2024

Cited by 2 | Viewed by 1618

Abstract

Cadherins are cell–cell adhesion proteins which have been strongly implicated in cancer invasion, dissemination and metastasis capacity; thus, they are key players in the epithelial-to-mesenchymal transition (EMT) program. However, their role in glioblastoma (GBM), a primary central nervous system aggressive tumor, remains to [...] Read more.

Cadherins are cell–cell adhesion proteins which have been strongly implicated in cancer invasion, dissemination and metastasis capacity; thus, they are key players in the epithelial-to-mesenchymal transition (EMT) program. However, their role in glioblastoma (GBM), a primary central nervous system aggressive tumor, remains to be clarified. N-, E- and P-cadherin expression was analyzed on a large series of GBMs, characterized with clinical, imaging and neuropathological parameters, as well as with patients’ survival data. In addition, cadherins’ expression was studied in match-recurrent cases. Using TCGA data, cadherin expression profiles were also evaluated according to GBM transcription subtypes. N-cadherin expression was observed in 81.5% of GBM, followed by E-cadherin in 31% and P-cadherin in 20.8%. Upon tumor recurrence, P-cadherin was the only significantly upregulated cadherin compared with the primary tumor, being positive in 65.8% of the cases. Actually, P-cadherin gain was observed in 51.4% of matched primary-recurrent cases. Cadherins’ co-expression was also explored. Interestingly, E- and N-cadherin co-expression identified a GBM subgroup with frequent epithelial differentiation and a significant survival benefit. On the other hand, subgroups with P-cadherin expression carried the worse prognosis. P- and N-cadherin co-expression correlated with the presence of a mesenchymal phenotype. Expressions of isolated P-cadherin or E- and P-cadherin co-expression were associated with imaging characteristics of aggressiveness, to highly heterogeneous tumors, an d to worse patient survival. Classical cadherins co-expression subgroups present consistent clinical, imaging, neuropathological and survival differences, which probably reflect different states of an EMT-like program in GBM. Full article

(This article belongs to the Topic Findings, Insights and Perspectives on Central Nervous System Tumors)

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21 pages, 2116 KiB  

Open AccessArticle

Genetic Prognostic Factors in Adult Diffuse Gliomas: A 10-Year Experience at a Single Institution

by Amir Barzegar Behrooz, Hadi Darzi Ramandi, Hamid Latifi-Navid, Payam Peymani, Rahil Tarharoudi, Nasrin Momeni, Mohammad Mehdi Sabaghpour Azarian, Sherif Eltonsy, Ahmad Pour-Rashidi and Saeid Ghavami

Cancers 2024, 16(11), 2121; https://doi.org/10.3390/cancers16112121 - 1 Jun 2024

Cited by 3 | Viewed by 2413

Abstract

Gliomas are primary brain lesions involving cerebral structures without well-defined boundaries and constitute the most prevalent central nervous system (CNS) neoplasms. Among gliomas, glioblastoma (GB) is a glioma of the highest grade and is associated with a grim prognosis. We examined how clinical [...] Read more.

Gliomas are primary brain lesions involving cerebral structures without well-defined boundaries and constitute the most prevalent central nervous system (CNS) neoplasms. Among gliomas, glioblastoma (GB) is a glioma of the highest grade and is associated with a grim prognosis. We examined how clinical variables and molecular profiles may have affected overall survival (OS) over the past ten years. A retrospective study was conducted at Sina Hospital in Tehran, Iran and examined patients with confirmed glioma diagnoses between 2012 and 2020. We evaluated the correlation between OS in GB patients and sociodemographic as well as clinical factors and molecular profiling based on IDH1, O-6-Methylguanine-DNA Methyltransferase (MGMT), TERTp, and epidermal growth factor receptor (EGFR) amplification (EGFR-amp) status. Kaplan–Meier and multivariate Cox regression models were used to assess patient survival. A total of 178 patients were enrolled in the study. The median OS was 20 months, with a 2-year survival rate of 61.0%. Among the 127 patients with available IDH measurements, 100 (78.7%) exhibited mutated IDH1 (IDH1-mut) tumors. Of the 127 patients with assessed MGMT promoter methylation (MGMTp-met), 89 (70.1%) had MGMT methylated tumors. Mutant TERTp (TERTp-mut) was detected in 20 out of 127 cases (15.7%), while wildtype TERTp (wildtype TERTp-wt) was observed in 107 cases (84.3%). Analyses using multivariable models revealed that age at histological grade (p < 0.0001), adjuvant radiotherapy (p < 0.018), IDH1 status (p < 0.043), and TERT-p status (p < 0.014) were independently associated with OS. Our study demonstrates that patients with higher tumor histological grades who had received adjuvant radiotherapy exhibited IDH1-mut or presented with TERTp-wt experienced improved OS. Besides, an interesting finding showed an association between methylation of MGMTp and TERTp status with tumor location. Full article

(This article belongs to the Topic Findings, Insights and Perspectives on Central Nervous System Tumors)

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13 pages, 1233 KiB  

Open AccessSystematic Review

Dexamethasone in Patients with Glioblastoma: A Systematic Review and Meta-Analysis

by Pierre Scheffler, Christian Fung, Shahan Momjian, Dominik Koessinger, Levin Häni, Nicolas Neidert, Jakob Straehle, Florian Volz, Oliver Schnell, Jürgen Beck and Amir El Rahal

Cancers 2024, 16(7), 1393; https://doi.org/10.3390/cancers16071393 - 1 Apr 2024

Cited by 2 | Viewed by 3465

Abstract

Objective: Glioblastomas are the most common primary central nervous system (CNS) tumors. Although modern management strategies have modestly improved overall survival, the prognosis remains dismal, with treatment side effects often impinging on the clinical course. Glioblastomas cause neurological dysfunction by infiltrating CNS tissue [...] Read more.

Objective: Glioblastomas are the most common primary central nervous system (CNS) tumors. Although modern management strategies have modestly improved overall survival, the prognosis remains dismal, with treatment side effects often impinging on the clinical course. Glioblastomas cause neurological dysfunction by infiltrating CNS tissue and via perifocal oedema formation. The administration of steroids such as dexamethasone is thought to alleviate symptoms by reducing oedema. However, despite its widespread use, the evidence for the administration of dexamethasone is limited and conflicting. Therefore, we aimed to review the current evidence concerning the use and outcomes of dexamethasone in patients with glioblastoma. Methods: We performed a systematic review and meta-analysis according to the PRISMA-P guidelines. We performed a restricted search using the keywords “Dexamethasone” and “Glioblastoma” on PubMed, Web of Science, Cochrane Library, and Academic Search Premier. We included studies reporting on overall survival (OS) and progression-free survival (PFS) in glioblastoma patients receiving higher or lower dexamethasone doses. The risk of bias was assessed using ROBINS-I. We performed a meta-analysis using a random effects model for OS and PFS. Results: Twenty-two retrospective studies were included. Higher doses of dexamethasone were associated with poorer OS (hazard ratio 1.62, confidence interval 1.40–1.88) and PFS (1.49, 1.23–1.81). OS remained worse even when studies corrected for clinical status (1.52, 1.38–1.67). Conclusion: Despite the widespread use of dexamethasone in glioblastoma patients, its use is correlated with worse long-term outcomes. Consequently, Dexamethasone administration should be restricted to selected symptomatic patients. Future prospective studies are crucial to confirm these findings. Full article

(This article belongs to the Topic Findings, Insights and Perspectives on Central Nervous System Tumors)

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17 pages, 2996 KiB  

Open AccessArticle

Revealing Pan-Histology Immunomodulatory Targets in Pediatric Central Nervous System Tumors

by Robert T. Galvin, Sampreeti Jena, Danielle Maeser, Robert Gruener and R. Stephanie Huang

Cancers 2023, 15(22), 5455; https://doi.org/10.3390/cancers15225455 - 17 Nov 2023

Cited by 1 | Viewed by 1686

Abstract

Background: The application of immunotherapy for pediatric CNS malignancies has been limited by the poorly understood immune landscape in this context. The aim of this study was to uncover the mechanisms of immune suppression common among pediatric brain tumors. Methods: We apply an [...] Read more.

Background: The application of immunotherapy for pediatric CNS malignancies has been limited by the poorly understood immune landscape in this context. The aim of this study was to uncover the mechanisms of immune suppression common among pediatric brain tumors. Methods: We apply an immunologic clustering algorithm validated by The Cancer Genome Atlas Project to an independent pediatric CNS transcriptomic dataset. Within the clusters, the mechanisms of immunosuppression are explored via tumor microenvironment deconvolution and survival analyses to identify relevant immunosuppressive genes with translational relevance. Results: High-grade diseases fall predominantly within an immunosuppressive subtype (C4) that independently lowers overall survival time and where common immune checkpoints (e.g., PDL1, CTLA4) are less relevant. Instead, we identify several alternative immunomodulatory targets with relevance across histologic diseases. Specifically, we show how the mechanism of EZH2 inhibition to enhance tumor immunogenicity in vitro via the upregulation of MHC class 1 is applicable to a pediatric CNS oncologic context. Meanwhile, we identify that the C3 (inflammatory) immune subtype is more common in low-grade diseases and find that immune checkpoint inhibition may be an effective way to curb progression for this subset. Conclusions: Three predominant immunologic clusters are identified across pediatric brain tumors. Among high-risk diseases, the predominant immune cluster is associated with recurrent immunomodulatory genes that influence immune infiltrate, including a subset that impacts survival across histologies. Full article

(This article belongs to the Topic Findings, Insights and Perspectives on Central Nervous System Tumors)

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22 pages, 402 KiB  

Open AccessEditor’s ChoiceReview

Recurrent Glioblastoma: A Review of the Treatment Options

by Maria Angeles Vaz-Salgado, María Villamayor, Víctor Albarrán, Víctor Alía, Pilar Sotoca, Jesús Chamorro, Diana Rosero, Ana M. Barrill, Mercedes Martín, Eva Fernandez, José Antonio Gutierrez, Luis Mariano Rojas-Medina and Luis Ley

Cancers 2023, 15(17), 4279; https://doi.org/10.3390/cancers15174279 - 26 Aug 2023

Cited by 47 | Viewed by 9558

Abstract

Glioblastoma is a disease with a poor prognosis. Multiple efforts have been made to improve the long-term outcome, but the 5-year survival rate is still 5–10%. Recurrence of the disease is the usual way of progression. In this situation, there is no standard [...] Read more.

Glioblastoma is a disease with a poor prognosis. Multiple efforts have been made to improve the long-term outcome, but the 5-year survival rate is still 5–10%. Recurrence of the disease is the usual way of progression. In this situation, there is no standard treatment. Different treatment options can be considered. Among them would be reoperation or reirradiation. There are different studies that have assessed the impact on survival and the selection of patients who may benefit most from these strategies. Chemotherapy treatments have also been considered in several studies, mainly with alkylating agents, with data mostly from phase II studies. On the other hand, multiple studies have been carried out with target-directed treatments. Bevacizumab, a monoclonal antibody with anti-angiogenic activity, has demonstrated activity in several studies, and the FDA has approved it for this indication. Several other TKI drugs have been evaluated in this setting, but no clear benefit has been demonstrated. Immunotherapy treatments have been shown to be effective in other types of tumors, and several studies have evaluated their efficacy in this disease, both immune checkpoint inhibitors, oncolytic viruses, and vaccines. This paper reviews data from different studies that have evaluated the efficacy of different forms of relapsed glioblastoma. Full article

(This article belongs to the Topic Findings, Insights and Perspectives on Central Nervous System Tumors)

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