Acquired drug resistance in glioblastoma (GBM) presents a major clinical challenge and is a key factor contributing to abysmal prognosis, with less than 15 months median overall survival. Aggressive chemotherapy with the frontline therapeutic, temozolomide (TMZ), ultimately fails to kill residual highly invasive tumor cells after surgical resection and radiotherapy. Here, a 3D engineered model of acquired TMZ resistance is reported using two isogenically matched sets of GBM cell lines encapsulated in gelatin methacrylol hydrogels. Response of TMZ-resistant versus TMZ-sensitive GBM cell lines within the gelatin-based extracellular matrix platform is benchmarked and drug response at physiologically relevant TMZ concentrations is further validated. The changes in drug sensitivity, cell invasion, and matrix-remodeling cytokine production are shown as the result of acquired TMZ resistance. This platform lays the foundation for future investigations targeting key elements of the GBM tumor microenvironment to combat GBM's devastating impact by advancing the understanding of GBM progression and treatment response to guide the development of novel treatment strategies.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11518645 | PMC |
| http://dx.doi.org/10.1002/adhm.202400779 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In Silico and In Vitro Study of mRNA Biomarkers for Glioblastoma Multiforme Resistance to Temozolomide (TMZ): The Association with Stemness.
Asian Pac J Cancer Prev
December 2024
Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Background: Glioblastoma multiforme (GBM) is an aggressive brain tumor that primarily affects adults. The Stupp Protocol, which includes surgical resection, chemoradiation, and monotherapy with temozolomide (TMZ), is the standard treatment regimen for GBM. However, repeated use of TMZ leads to resistance in GBM cells, resulting in a poor prognosis for patients.
View Article and Find Full Text PDFThe novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma.
Neuro Oncol
December 2024
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago IL.
Article Synopsis
- Acquired resistance to temozolomide (TMZ) in glioblastoma patients, particularly those with DNA mismatch repair deficiencies, limits treatment effectiveness, prompting research into the new drug KL-50, which targets cancer cells in an MMR-independent manner.
- In studies, KL-50 significantly improved the median survival of mice with both naive and post-TMZ glioblastoma xenografts, showcasing its potential as a superior treatment option.
- Results indicate KL-50 may be particularly effective in MGMT and MMR-deficient tumors, offering hope for better management of recurrent glioblastoma after initial TMZ therapy.
Higher isoform of hnRNPA1 confer Temozolomide resistance in U87MG & LN229 glioma cells.
J Neurooncol
January 2025
Molecular Cancer Genetics and Signal Transduction Laboratory, Dr. B.R Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Gate No. 1, Vishwavidyalaya Marg, Mall Road, 44, AH2, Delhi, 110007, India.
Background: Gliblastoma is a malignant brain tumor; despite available treatment modalities, the tumor reoccurrence rate persist in the currently prescribed Temozolomide chemotherapy. Study aimed to study the inquisitive role of RNA binding splice factor protein hnRNPA1 in promoting glioma resistance against Temozolomide drug and therapeutic insights.
Methods: In this study two non-expressing O-methylguanine-DNA methyltransferase (MGMT) glioma cell lines U87MG & LN229.
Novel strategies to overcome chemoresistance in human glioblastoma.
Biochem Pharmacol
December 2024
Beijing Key Laboratory of Environmental and Viral Oncology, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China. Electronic address:
Temozolomide (TMZ) is currently the first-line chemotherapeutic agent for the treatment of glioblastoma multiforme (GBM). However, the inherent heterogeneity of GBM often results in suboptimal outcomes, particularly due to varying degrees of resistance to TMZ. Over the past several decades, O-methylguanine-DNA methyltransferase (MGMT)-mediated DNA repair pathway has been extensively investigated as a target to overcome TMZ resistance.
View Article and Find Full Text PDFMELATONIN ENHANCES TEMOZOLOMIDE-INDUCED APOPTOSIS IN GLIOBLASTOMA AND NEUROBLASTOMA CELLS.
Exp Oncol
October 2024
Department of Medical Biology, Faculty of Medicine, Trakya University, Edirne, Turkey.
Article Synopsis
- The study investigates the effects of melatonin (MEL) combined with temozolomide (TMZ) on glioblastoma and neuroblastoma cancer cell lines, aiming to understand how this combination affects cell viability and resistance.
- Results reveal that the MEL and TMZ combination significantly decreases cancer cell viability and increases apoptosis compared to other treatments, highlighting a potential strategy to counteract drug resistance in these cancers.
- The findings suggest that this combination therapy upregulates genes involved in antioxidant defense and DNA repair, indicating a possible mechanism through which MEL enhances the efficacy of TMZ.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!