Trial reportThe Journal of clinical investigation2014
Gene therapy enhances chemotherapy tolerance and efficacy in glioblastoma patients.
Trial report in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00669669 (Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cells for Patients With Malignant Gliomas), which is not on this map. Cited by 57 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cells for Patients With Malignant Gliomas
Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 101 citations in OpenAlex.
- Personalised therapeutic approaches to glioblastoma: A systematic review.Frontiers in medicine · 2023Pooled it
- Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of emerging developments in the management of newly diagnosed glioblastoma.Journal of neuro-oncology · 2020Pooled it
- Systemic delivery of phagocytosis-shielded retroviral vectors enables in vivo HSC gene therapy for sickle cell disease.Cell stem cell · 2026Article
- Article
- Mapping the global research landscape and innovations on elderly glioma: a bibliometric analysis.Frontiers in oncology · 2026Article
- Revisiting an old therapy for new, promising combinations: Biology and perspectives of lomustine in glioma treatment.Neuro-oncology · 2025Review
- Identifying active and inhibitor-resistant MGMT variants for gene therapy.American journal of human genetics · 2025Article
- Clinical hematopoietic stem cell-based gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Rational therapeutic targeting of myeloid cells in glioblastoma: challenges and perspectives.Frontiers in immunology · 2025Review
- The DNA Alkyltransferase Family of DNA Repair Proteins: Common Mechanisms, Diverse Functions.International journal of molecular sciences · 2023Review
- The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in glioma.Drug delivery · 2023Article
- Current Approaches to Epigenetic Therapy.Epigenomes · 2023Review
- Article
- Stable HIV decoy receptor expression after in vivo HSC transduction in mice and NHPs: Safety and efficacy in protection from SHIV.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Systematic Review of Pediatric Brain Tumors in Neurofibromatosis Type 1: Status of Gene Therapy.Cureus · 2022Review
- Safe and efficientMolecular therapy. Methods & clinical development · 2022Article
- A combined treatment regimen of MGMT-modified γδ T cells and temozolomide chemotherapy is effective against primary high grade gliomas.Scientific reports · 2021Article
- The role of mRNA in the development, diagnosis, treatment and prognosis of neural tumors.Molecular cancer · 2021Review
- Hematopoietic stem cell gene therapy targeting TGFβ enhances the efficacy of irradiation therapy in a preclinical glioblastoma model.Journal for immunotherapy of cancer · 2021Article
- In Vivo HSC Gene Therapy Using a Bi-modular HDAd5/35++ Vector Cures Sickle Cell Disease in a Mouse Model.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
Corrections and comments
- Commented on by
Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundTemozolomide (TMZ) is one of the most potent chemotherapy agents for the treatment of glioblastoma. Unfortunately, almost half of glioblastoma tumors are TMZ resistant due to overexpression of methylguanine methyltransferase (MGMT(hi)). Coadministration of O6-benzylguanine (O6BG) can restore TMZ sensitivity, but causes off-target myelosuppression. Here, we conducted a prospective clinical trial to test whether gene therapy to confer O6BG resistance in hematopoietic stem cells (HSCs) improves chemotherapy tolerance and outcome.
methodsWe enrolled 7 newly diagnosed glioblastoma patients with MGMT(hi) tumors. Patients received autologous gene-modified HSCs following single-agent carmustine administration. After hematopoietic recovery, patients underwent O6BG/TMZ chemotherapy in 28-day cycles. Serial blood samples and tumor images were collected throughout the study. Chemotherapy tolerance was determined by the observed myelosuppression and recovery following each cycle. Patient-specific biomathematical modeling of tumor growth was performed. Progression-free survival (PFS) and overall survival (OS) were also evaluated.
resultsGene therapy permitted a significant increase in the mean number of tolerated O6BG/TMZ cycles (4.4 cycles per patient, P < 0.05) compared with historical controls without gene therapy (n = 7 patients, 1.7 cycles per patient). One patient tolerated an unprecedented 9 cycles and demonstrated long-term PFS without additional therapy. Overall, we observed a median PFS of 9 (range 3.5-57+) months and OS of 20 (range 13-57+) months. Furthermore, biomathematical modeling revealed markedly delayed tumor growth at lower cumulative TMZ doses in study patients compared with patients that received standard TMZ regimens without O6BG.
conclusionThese data support further development of chemoprotective gene therapy in combination with O6BG and TMZ for the treatment of glioblastoma and potentially other tumors with overexpression of MGMT.
trial registrationClinicaltrials.gov NCT00669669.
fundingR01CA114218, R01AI080326, R01HL098489, P30DK056465, K01DK076973, R01HL074162, R01CA164371, R01NS060752, U54CA143970.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.