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Recent Molecular Research for Glioblastoma
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Recent Molecular Research for Glioblastoma

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: closed (10 June 2024) | Viewed by 4345

Special Issue Editor

Dr. Jui-Chieh Chen

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Guest Editor
Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan
Interests: oral squamous cell carcinoma; glioblastoma

Special Issue Information

Dear Colleagues,

Glioblastoma multiforme (GBM) is a highly aggressive and lethal brain cancer with limited treatment options that offer only modest survival benefits. The heterogeneity of GBM poses a significant challenge to treatment, and the blood-brain barrier limits the effectiveness of systemic therapies. As such, new therapeutic approaches are urgently needed to improve the prognosis of GBM patients.

In this special issue, we aim to stimulate research and enhance our understanding of the molecular and genetic mechanisms underlying GBM development and progression and their impact on disease management. We welcome research submissions that explore new therapeutic targets and strategies, including personalized medicine and targeted drug delivery, such as the use of nanoparticles. These particles have the potential to penetrate the blood-brain barrier and deliver therapeutic agents directly to the tumor sites, enhancing their anti-tumor activity. Additionally, we encourage studies that investigate the tumor microenvironment's role in GBM growth and resistance to therapy.

We hope that this special issue will provide a platform for researchers to share their latest findings and insights into the complex biology of GBM and explore new avenues for improving the diagnosis, treatment, and survival of GBM patients.

Dr. Jui-Chieh Chen
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 multiforme (GBM)
  • personalized medicine
  • targeted drug delivery
  • nanoparticles
  • tumor microenvironment
  • drug resistance
  • non-coding RNAs
  • diagnosis and treatment

Published Papers (3 papers)

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Research

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24 pages, 6005 KiB  
Article
Using a Dual CRISPR/Cas9 Approach to Gain Insight into the Role of LRP1B in Glioblastoma
by Joana Peixoto, Catarina Príncipe, Ana Pestana, Hugo Osório, Marta Teixeira Pinto, Hugo Prazeres, Paula Soares and Raquel T. Lima
Int. J. Mol. Sci. 2023, 24(14), 11285; https://doi.org/10.3390/ijms241411285 - 10 Jul 2023
Cited by 3 | Viewed by 1763
Abstract
LRP1B remains one of the most altered genes in cancer, although its relevance in cancer biology is still unclear. Recent advances in gene editing techniques, particularly CRISPR/Cas9 systems, offer new opportunities to evaluate the function of large genes, such as LRP1B. Using [...] Read more.
LRP1B remains one of the most altered genes in cancer, although its relevance in cancer biology is still unclear. Recent advances in gene editing techniques, particularly CRISPR/Cas9 systems, offer new opportunities to evaluate the function of large genes, such as LRP1B. Using a dual sgRNA CRISPR/Cas9 gene editing approach, this study aimed to assess the impact of disrupting LRP1B in glioblastoma cell biology. Four sgRNAs were designed for the dual targeting of two LRP1B exons (1 and 85). The U87 glioblastoma (GB) cell line was transfected with CRISPR/Cas9 PX459 vectors. To assess LRP1B-gene-induced alterations and expression, PCR, Sanger DNA sequencing, and qRT-PCR were carried out. Three clones (clones B9, E6, and H7) were further evaluated. All clones presented altered cellular morphology, increased cellular and nuclear size, and changes in ploidy. Two clones (E6 and H7) showed a significant decrease in cell growth, both in vitro and in the in vivo CAM assay. Proteomic analysis of the clones’ secretome identified differentially expressed proteins that had not been previously associated with LRP1B alterations. This study demonstrates that the dual sgRNA CRISPR/Cas9 strategy can effectively edit LRP1B in GB cells, providing new insights into the impact of LRP1B deletions in GBM biology. Full article
(This article belongs to the Special Issue Recent Molecular Research for Glioblastoma)
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16 pages, 5979 KiB  
Article
ADAM17 Confers Temozolomide Resistance in Human Glioblastoma Cells and miR-145 Regulates Its Expression
by Jen-Tsung Yang, I-Neng Lee, Cheng Huang, Hsiu-Chen Huang, Yu-Ping Wu, Zhi-Yong Chong and Jui-Chieh Chen
Int. J. Mol. Sci. 2023, 24(9), 7703; https://doi.org/10.3390/ijms24097703 - 22 Apr 2023
Cited by 4 | Viewed by 1861
Abstract
Glioblastoma (GBM) is a malignant brain tumor, commonly treated with temozolomide (TMZ). Upregulation of A disintegrin and metalloproteinases (ADAMs) is correlated to malignancy; however, whether ADAMs modulate TMZ sensitivity in GBM cells remains unclear. To explore the role of ADAMs in TMZ resistance, [...] Read more.
Glioblastoma (GBM) is a malignant brain tumor, commonly treated with temozolomide (TMZ). Upregulation of A disintegrin and metalloproteinases (ADAMs) is correlated to malignancy; however, whether ADAMs modulate TMZ sensitivity in GBM cells remains unclear. To explore the role of ADAMs in TMZ resistance, we analyzed changes in ADAM expression following TMZ treatment using RNA sequencing and noted that ADAM17 was markedly upregulated. Hence, we established TMZ-resistant cell lines to elucidate the role of ADAM17. Furthermore, we evaluated the impact of ADAM17 knockdown on TMZ sensitivity in vitro and in vivo. Moreover, we predicted microRNAs upstream of ADAM17 and transfected miRNA mimics into cells to verify their effects on TMZ sensitivity. Additionally, the clinical significance of ADAM17 and miRNAs in GBM was analyzed. ADAM17 was upregulated in GBM cells under serum starvation and TMZ treatment and was overexpressed in TMZ-resistant cells. In in vitro and in vivo models, ADAM17 knockdown conferred greater TMZ sensitivity. miR-145 overexpression suppressed ADAM17 and sensitized cells to TMZ. ADAM17 upregulation and miR-145 downregulation in clinical specimens are associated with disease progression and poor prognosis. Thus, miR-145 enhances TMZ sensitivity by inhibiting ADAM17. These findings offer insights into the development of therapeutic approaches to overcome TMZ resistance. Full article
(This article belongs to the Special Issue Recent Molecular Research for Glioblastoma)
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Review

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14 pages, 2196 KiB  
Review
CAR-T Cells Therapy in Glioblastoma: A Systematic Review on Molecular Targets and Treatment Strategies
by Edoardo Agosti, Alexandru Garaba, Sara Antonietti, Tamara Ius, Marco Maria Fontanella, Marco Zeppieri and Pier Paolo Panciani
Int. J. Mol. Sci. 2024, 25(13), 7174; https://doi.org/10.3390/ijms25137174 (registering DOI) - 29 Jun 2024
Viewed by 142
Abstract
The most common primary brain tumor is glioblastoma (GBM), yet the current therapeutic options for this disease are not promising. Although immunotherapeutic techniques have shown poor success in GBM thus far despite efforts, new developments provide optimism. One of these developments is chimeric [...] Read more.
The most common primary brain tumor is glioblastoma (GBM), yet the current therapeutic options for this disease are not promising. Although immunotherapeutic techniques have shown poor success in GBM thus far despite efforts, new developments provide optimism. One of these developments is chimeric antigen receptor (CAR)-T cell treatment, which includes removing and genetically modifying autologous T cells to produce a receptor that targets a GBM antigen before reintroducing the cells into the patient’s body. A number of preclinical studies have produced encouraging results, which have led to the start of clinical trials assessing these CAR-T cell treatments for GBM and other brain tumors. Although results in tumors such as diffuse intrinsic pontine gliomas and lymphomas have been promising, preliminary findings in GBM have not produced any clinical benefits. The paucity of particular antigens in GBM, their inconsistent expression patterns, and the possible immunoediting-induced loss of these antigens after antigen-targeted therapy are some possible causes for this discrepancy. The goal of this systematic literature review is to assess potential approaches for creating CAR-T cells that are more effective for this indication, as well as the clinical experiences that are already being had with CAR-T cell therapy in GBM. Up until 9 May 2024, a thorough search was carried out across the three main medical databases: PubMed, Web of Science, and Scopus. Relevant Medical Subject Heading (MeSH) terms and keywords associated with “glioblastoma”, “CAR-T”, “T cell therapy”, “overall survival”, and “progression free survival” were employed in the search approach. Preclinical and clinical research on the application of CAR-T cells as a therapeutic approach for GBM are included in the review. A total of 838 papers were identified. Of these, 379 articles were assessed for eligibility, resulting in 8 articles meeting the inclusion criteria. The included studies were conducted between 2015 and 2023, with a total of 151 patients enrolled. The studies varied in CAR-T cell types. EGFRvIII CAR-T cells were the most frequently investigated, used in three studies (37.5%). Intravenous delivery was the most common method of delivery (62.5%). Median OS ranged from 5.5 to 11.1 months across the studies. PFS was reported in only two studies, with values of 7.5 months and 1.3 months. This systematic review highlights the evolving research on CAR-T cell therapy for GBM, emphasizing its potential despite challenges. Targeting antigens like EGFRvIII and IL13Rα2 shows promise in treating recurrent GBM. However, issues such as antigen escape, tumor heterogeneity, and immunosuppression require further optimization. Innovative delivery methods, combination therapies, and personalized approaches are crucial for enhancing CAR-T cell efficacy. Ongoing research is essential to refine these therapies and improve outcomes for GBM patients. Full article
(This article belongs to the Special Issue Recent Molecular Research for Glioblastoma)
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