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Cancers
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Novel Insights into Glioblastoma and Brain Metastases
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Novel Insights into Glioblastoma and Brain Metastases

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

Deadline for manuscript submissions: 31 December 2024 | Viewed by 9741

Special Issue Editor

Prof. Dr. Sanjay K. Srivastava

E-Mail Website
Guest Editor
Department of Immunotherapeutics and Biotechnology, Texas Tech University Health Sciences Center, 1718 Pine Street, Abilene, TX 79601, USA
Interests: development of phytochemicals for cancer prevention and therapeutics; targeting STAT-3, NF-kB, HER2, MCL-1, AKT/FOXO, GLI1/2, and related signaling pathways with agents such as capsaicin, piperlongumine, penfluridol, isothiocyanates, diindolylmethane, panabinostat, cucurbitacin B, and deguelin in pancreatic, ovarian, breast, melanoma, and brain cancer; drug repurposing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glioblastoma is an aggressive grade IV brain tumor leading to severe fatalities globally. Moreover, several cancers lead to brain metastasis which is a major cause of mortality. Tackling these conditions has several challenges, with the most important being the blood–brain barrier (BBB) permeability. Significant research is required to overcome these challenges. With surgery and radiation therapy being the major treatment strategy for brain tumors, intensive research has also been conducted on chemotherapies. Targeted therapies are currently being developed with beneficial effects in cancers such as colorectal, breast, lung, and melanoma. Radiation therapy has also proven to be quite successful against brain metastasis. Thus, in this Special Issue, we invite you to contribute your work concerning glioblastoma, novel insights into its treatment and management, and different cancers leading to brain metastasis. This Special Issue aims to highlight all types of work, such as clinical, pre-clinical, translational, and basic research. We invite both original research articles and review articles in this Special Issue. This critical topic would appeal to a number of scientists and clinicians in the field. The articles may include (but are not limited to) treatment, management, diagnosis, clinical trials, and molecular insights for glioblastoma and brain metastasis caused by different cancers such as breast, melanoma, renal, lung, colorectal, etc.

Prof. Dr. Sanjay K. Srivastava
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glioblastoma
  • brain metastasis
  • surgery
  • radiation
  • chemotherapy
  • blood–brain barrier
  • immunotherapy
  • novel targets
  • oncogenes
  • tumor heterogeneity
  • drug discovery

Published Papers (6 papers)

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Research

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19 pages, 4390 KiB  
Article
Proline Metabolism in WHO G4 Gliomas Is Altered as Compared to Unaffected Brain Tissue
by Magdalena M. Sawicka, Karol Sawicki, Marek Jadeszko, Katarzyna Bielawska, Elżbieta Supruniuk, Joanna Reszeć, Izabela Prokop-Bielenia, Barbara Polityńska, Mateusz Jadeszko, Magdalena Rybaczek, Eryk Latoch, Krzysztof Gorbacz, Tomasz Łysoń and Wojciech Miltyk
Cancers 2024, 16(2), 456; https://doi.org/10.3390/cancers16020456 - 21 Jan 2024
Viewed by 855
Abstract
Proline metabolism has been identified as a significant player in several neoplasms, but knowledge of its role in gliomas is limited despite it providing a promising line of pursuit. Data on proline metabolism in the brain are somewhat historical. This study aims to [...] Read more.
Proline metabolism has been identified as a significant player in several neoplasms, but knowledge of its role in gliomas is limited despite it providing a promising line of pursuit. Data on proline metabolism in the brain are somewhat historical. This study aims to investigate alterations of proline metabolism in gliomas of WHO grade 4 (GG4) in the context of the brain. A total of 20 pairs of samples were studied, consisting of excised tumor and unaffected brain tissue, obtained when partial brain resection was required to reach deep-seated lesions. Levels of proline oxidase/proline dehydrogenase (POX/PRODH), Δ1-pyrroline-5-carboxylate reductases (PYCR1/2/3), prolidase (PEPD), and metalloproteinases (MMP-2, MMP-9) were assessed, along with the concentration of proline and proline-related metabolites. In comparison to normal brain tissue, POX/PRODH expression in GG4 was found to be suppressed, while PYCR1 expression and activity of PEPD, MMP-2, and -9 were upregulated. The GG4 proline concentration was 358% higher. Hence, rewiring of the proline metabolism in GG4 was confirmed for the first time, with a low-POX/PRODH/high-PYCR profile. High PEPD and MMPs activity is in keeping with GG4-increased collagen turnover and local aggressiveness. Further studies on the mechanisms of the interplay between altered proline metabolism and the GG4 microenvironment are warranted. Full article
(This article belongs to the Special Issue Novel Insights into Glioblastoma and Brain Metastases)
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11 pages, 1533 KiB  
Article
Intramedullary Spinal Cord Tumors: Whole-Genome Sequencing to Assist Management and Prognosis
by Miguel Mayol del Valle, Bryan Morales, Brandon Philbrick, Segun Adeagbo, Subir Goyal, Sarah Newman, Natasha L. Frontera, Edjah Nduom, Jeffrey Olson, Stewart Neill and Kimberly Hoang
Cancers 2024, 16(2), 404; https://doi.org/10.3390/cancers16020404 - 18 Jan 2024
Viewed by 809
Abstract
Intramedullary spinal cord tumors (IMSCTs) harbor unique genetic mutations which may play a role in prognostication and management. To this end, we present the largest cohort of IMSCTs with genetic characterization in the literature from our multi-site institutional registry. A total of 93 [...] Read more.
Intramedullary spinal cord tumors (IMSCTs) harbor unique genetic mutations which may play a role in prognostication and management. To this end, we present the largest cohort of IMSCTs with genetic characterization in the literature from our multi-site institutional registry. A total of 93 IMSCT patient records were reviewed from the years 1999 to 2020. Out of these, 61 complied with all inclusion criteria, 14 of these patients had undergone genetic studies with 8 undergoing whole-genomic sequencing. Univariate analyses were used to assess any factors associated with progression-free survival (PFS) using the Cox proportional hazards model. Firth’s penalized likelihood approach was used to account for the low event rates. Fisher’s exact test was performed to compare whole-genome analyses and specific gene mutations with progression. PFS (months) was given as a hazard ratio. Only the absence of copy neutral loss of heterozygosity (LOH) was shown to be significant (0.05, p = 0.008). Additionally, higher risk of recurrence/progression was associated with LOH (p = 0.0179). Our results suggest LOH as a genetic predictor of shorter progression-free survival, particularly within ependymoma and glioblastoma tumor types. Further genomic research with larger multi-institutional datasets should focus on these mutations as possible prognostic factors. Full article
(This article belongs to the Special Issue Novel Insights into Glioblastoma and Brain Metastases)
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16 pages, 2454 KiB  
Article
In Vitro and In Vivo Drug-Response Profiling Using Patient-Derived High-Grade Glioma
by Robin G. Rajan, Virneliz Fernandez-Vega, Jantzen Sperry, Jonathan Nakashima, Long H. Do, Warren Andrews, Simina Boca, Rezwanul Islam, Sajeel A. Chowdhary, Jan Seldin, Glauco R. Souza, Louis Scampavia, Khalid A. Hanafy, Frank D. Vrionis and Timothy P. Spicer
Cancers 2023, 15(13), 3289; https://doi.org/10.3390/cancers15133289 - 22 Jun 2023
Cited by 2 | Viewed by 1965
Abstract
Background: Genomic profiling cannot solely predict the complexity of how tumor cells behave in their in vivo microenvironment and their susceptibility to therapies. The aim of the study was to establish a functional drug prediction model utilizing patient-derived GBM tumor samples for in [...] Read more.
Background: Genomic profiling cannot solely predict the complexity of how tumor cells behave in their in vivo microenvironment and their susceptibility to therapies. The aim of the study was to establish a functional drug prediction model utilizing patient-derived GBM tumor samples for in vitro testing of drug efficacy followed by in vivo validation to overcome the disadvantages of a strict pharmacogenomics approach. Methods: High-throughput in vitro pharmacologic testing of patient-derived GBM tumors cultured as 3D organoids offered a cost-effective, clinically and phenotypically relevant model, inclusive of tumor plasticity and stroma. RNAseq analysis supplemented this 128-compound screening to predict more efficacious and patient-specific drug combinations with additional tumor stemness evaluated using flow cytometry. In vivo PDX mouse models rapidly validated (50 days) and determined mutational influence alongside of drug efficacy. We present a representative GBM case of three tumors resected at initial presentation, at first recurrence without any treatment, and at a second recurrence following radiation and chemotherapy, all from the same patient. Results: Molecular and in vitro screening helped identify effective drug targets against several pathways as well as synergistic drug combinations of cobimetinib and vemurafenib for this patient, supported in part by in vivo tumor growth assessment. Each tumor iteration showed significantly varying stemness and drug resistance. Conclusions: Our integrative model utilizing molecular, in vitro, and in vivo approaches provides direct evidence of a patient’s tumor response drifting with treatment and time, as demonstrated by dynamic changes in their tumor profile, which may affect how one would address that drift pharmacologically. Full article
(This article belongs to the Special Issue Novel Insights into Glioblastoma and Brain Metastases)
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12 pages, 847 KiB  
Article
Preoperative Prognostic Index for Patients with Brain Metastases—A Population-Based Multi-Centre Study
by Rebecca Rootwelt Winther, Eva Skovlund, Joakim Stray Andreassen, Lisa Arvidsson, Jonathan Halvardson, Ole Solheim, Jiri Bartek, Stein Kaasa, Marianne Jensen Hjermstad and Einar Osland Vik-Mo
Cancers 2023, 15(12), 3174; https://doi.org/10.3390/cancers15123174 - 13 Jun 2023
Viewed by 1062
Abstract
Background: Brain metastases (BM) are common in cancer patients and are associated with high morbidity and mortality. Surgery is an option, but the optimal selection of patients for surgery is challenging and controversial. Current prognostication tools are not ideal for preoperative prognostication. By [...] Read more.
Background: Brain metastases (BM) are common in cancer patients and are associated with high morbidity and mortality. Surgery is an option, but the optimal selection of patients for surgery is challenging and controversial. Current prognostication tools are not ideal for preoperative prognostication. By using a reference population (derivation data set) and two external populations (validation data set) of patients who underwent surgery for BM, we aimed to create and validate a preoperative prognostic index. Methods: The derivation data set consists of 590 patients who underwent surgery for BM (2011–2018) at Oslo University Hospital. We identified variables associated with survival and created a preoperative prognostic index with four prognostic groups, which was validated on patients who underwent surgery for BM at Karolinska University Hospital and St. Olavs University Hospital during the same time period. To reduce over-fitting, we adjusted the index in accordance with our findings. Results: 438 patients were included in the validation data set. The preoperative prognostic index correctly divided patients into four true prognostic groups. The two prognostic groups with the poorest survival outcomes overlapped, and these were merged to create the adjusted preoperative prognostic index. Conclusion: We created a prognostic index for patients with BM that predicts overall survival preoperatively. This index might be valuable in supporting informed choice when considering surgery for BM. Full article
(This article belongs to the Special Issue Novel Insights into Glioblastoma and Brain Metastases)
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19 pages, 4229 KiB  
Article
Neuronal Cannabinoid CB1 Receptors Suppress the Growth of Melanoma Brain Metastases by Inhibiting Glutamatergic Signalling
by Carlos Costas-Insua, Marta Seijo-Vila, Cristina Blázquez, Sandra Blasco-Benito, Francisco Javier Rodríguez-Baena, Giovanni Marsicano, Eduardo Pérez-Gómez, Cristina Sánchez, Berta Sánchez-Laorden and Manuel Guzmán
Cancers 2023, 15(9), 2439; https://doi.org/10.3390/cancers15092439 - 24 Apr 2023
Viewed by 3427
Abstract
Melanoma is one of the deadliest forms of cancer. Most melanoma deaths are caused by distant metastases in several organs, especially the brain, the so-called melanoma brain metastases (MBMs). However, the precise mechanisms that sustain the growth of MBMs remain elusive. Recently, the [...] Read more.
Melanoma is one of the deadliest forms of cancer. Most melanoma deaths are caused by distant metastases in several organs, especially the brain, the so-called melanoma brain metastases (MBMs). However, the precise mechanisms that sustain the growth of MBMs remain elusive. Recently, the excitatory neurotransmitter glutamate has been proposed as a brain-specific, pro-tumorigenic signal for various types of cancers, but how neuronal glutamate shuttling onto metastases is regulated remains unknown. Here, we show that the cannabinoid CB1 receptor (CB1R), a master regulator of glutamate output from nerve terminals, controls MBM proliferation. First, in silico transcriptomic analysis of cancer-genome atlases indicated an aberrant expression of glutamate receptors in human metastatic melanoma samples. Second, in vitro experiments conducted on three different melanoma cell lines showed that the selective blockade of glutamatergic NMDA receptors, but not AMPA or metabotropic receptors, reduces cell proliferation. Third, in vivo grafting of melanoma cells in the brain of mice selectively devoid of CB1Rs in glutamatergic neurons increased tumour cell proliferation in concert with NMDA receptor activation, whereas melanoma cell growth in other tissue locations was not affected. Taken together, our findings demonstrate an unprecedented regulatory role of neuronal CB1Rs in the MBM tumour microenvironment. Full article
(This article belongs to the Special Issue Novel Insights into Glioblastoma and Brain Metastases)
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Review

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17 pages, 4428 KiB  
Review
m6A mRNA Modifications in Glioblastoma: Emerging Prognostic Biomarkers and Therapeutic Targets
by Gloria S. Xie and Hope T. Richard
Cancers 2024, 16(4), 727; https://doi.org/10.3390/cancers16040727 - 09 Feb 2024
Viewed by 1002
Abstract
Glioblastoma, the most common and aggressive primary brain tumor, is highly invasive and neurologically destructive. The mean survival for glioblastoma patients is approximately 15 months and there is no effective therapy to significantly increase survival times to date. The development of effective therapy [...] Read more.
Glioblastoma, the most common and aggressive primary brain tumor, is highly invasive and neurologically destructive. The mean survival for glioblastoma patients is approximately 15 months and there is no effective therapy to significantly increase survival times to date. The development of effective therapy including mechanism-based therapies is urgently needed. At a molecular biology level, N6-methyladenine (m6A) mRNA modification is the most abundant posttranscriptional RNA modification in mammals. Recent studies have shown that m6A mRNA modifications affect cell survival, cell proliferation, invasion, and immune evasion of glioblastoma. In addition, m6A mRNA modifications are critical for glioblastoma stem cells, which could initiate the tumor and lead to therapy resistance. These findings implicate the function of m6A mRNA modification in tumorigenesis and progression, implicating its value in prognosis and therapies of human glioblastoma. This review focuses on the potential clinical significance of m6A mRNA modifications in prognostic and therapeutics of glioblastoma. With the identification of small-molecule compounds that activate or inhibit components of m6A mRNA modifications, a promising novel approach for glioblastoma therapy is emerging. Full article
(This article belongs to the Special Issue Novel Insights into Glioblastoma and Brain Metastases)
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