Preoperative statin use is not associated with improvement in survival after glioblastoma surgery

Bhavsar, Shreyas; Hagan, Katherine; Arunkumar, Radha; Potylchansky, Y.; Grasu, Roxana; Dang, Anh; Carlson, Richard; Cowels, C.; Arnold, Benjamin; Rahlfs, Thomas F.; Lipski, Ian; Walsh, Caroline; Nguyen, Anh T.; Feng, Lei; Cata, Juan P.

doi:10.1016/j.jocn.2016.03.010

Cited by 22 publications

(16 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, micromolar concentrations of statins can cause induction of apoptosis in normal cells, such as primary cultures of neuronal brain cortices (44, 45) Our studies are distinguished from the prior studies, which were focused on established cell lines, like U87, which poorly represent BTICs, so may underestimate the value of these agents. Cohort studies have suggested contradictory conclusions with regard to correlation between use of preoperative statin use and decreased risk of glioma formation and mortality (46, 47). Due to the small number of patients, retrospective nature of these studies and more importantly, lack of sustained use of statins, further work is needed to understand the role of statins in glioblastoma therapy.…”

Section: Discussionmentioning

confidence: 99%

MYC-Regulated Mevalonate Metabolism Maintains Brain Tumor–Initiating Cells

Wang

Huang

et al. 2017

Cancer Research

View full text Add to dashboard Cite

Metabolic dysregulation drives tumor initiation in a subset of glioblastomas harboring isocitrate dehydrogenase (IDH) mutations, but metabolic alterations in glioblastomas with wildtype IDH are poorly understood. MYC promotes metabolic reprogramming in cancer, but targeting MYC has proven notoriously challenging. Here, we link metabolic dysregulation in patient-derived brain tumor initiating cells (BTICs) to a nexus between MYC and mevalonate signaling, which can be inhibited by statin or 6-fluoromevalonate treatment. BTICs preferentially express mevalonate pathway enzymes, which we find regulated by novel MYC binding sites, validating an additional transcriptional activation role of MYC in cancer metabolism. Targeting mevalonate activity attenuated RAS-ERK-dependent BTIC growth and self-renewal. In turn, mevalonate created a positive feed-forward loop to activate MYC signaling via induction of miR-33b. Collectively, our results argue that MYC mediates its oncogenic effects in part by altering mevalonate metabolism in glioma cells, suggesting a therapeutic strategy in this setting.

show abstract

Section: Discussionmentioning

confidence: 99%

MYC-Regulated Mevalonate Metabolism Maintains Brain Tumor–Initiating Cells

Wang

Huang

et al. 2017

Cancer Research

View full text Add to dashboard Cite

show abstract

“…While the effect on survival was highly significant and meaningful, most animals ultimately showed tumor progression and our search for a possible resistance mechanism revealed upregulation of key components of the cholesterol biosynthesis pathway in the response of glioblastoma cells to the combined treatment with dopamine receptor antagonists and radiation. A previous report had shown dependence of the survival of glioblastoma cells on cholesterol (25) but a potential beneficial impact of statin use in glioblastoma patients is currently discussed controversially (26)(27)(28)(29). We report here that QTP treatment but not irradiation alone led to upregulation of the key components of the cholesterol biosynthesis.…”

Section: Discussionmentioning

confidence: 52%

Combined Treatment with Dopamine Receptor Antagonists and Radiation Creates a Metabolic Vulnerability in Mouse Models of Glioblastoma

Saki

Bhat

Cheng

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Glioblastoma is the deadliest brain tumor in adults and the standard-of-care consists of surgery followed by radiation and treatment with temozolomide. Overall survival times for patients suffering from glioblastoma are unacceptably low indicating an unmet need for novel treatment options. MethodsUsing patient-derived glioblastoma lines and mouse models of glioblastoma we test the effect of radiation and the dopamine receptor antagonist on glioblastoma self-renewal in vitro and survival in vivo. A possible resistance mechanism is investigated using RNA-Sequencing. ResultsTreatment of glioma cells with the dopamine receptor antagonist quetiapine reduced glioma cell self-renewal in vitro and combined treatment of mice with quetiapine and radiation prolonged the survival of glioma-bearing animals. The combined treatment induced the expression of genes involved in cholesterol biosynthesis. This rendered the tumors vulnerable to simultaneous treatment with atorvastatin and further significantly prolonged the survival of the animals. ConclusionsOur results indicate high efficacy of a triple combination of quetiapine, atorvastatin and radiation against glioblastoma without increasing the toxicity of radiation. With both drugs readily available for clinical use our study could be rapidly translated into a clinical trial.

show abstract

“…However, the results of clinical studies are controversial. A recent study did not reveal a link between preoperative statin use and favorable survival prognosis in patients with glioblastoma [ 30 ]. In contrast, a different study revealed that pre-diagnostic long-term statin use correlated with favorable prognosis following glioblastoma diagnosis [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of pre-surgical serum lipid levels in patients with glioblastoma

Liang

Mao

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Accumulating evidence demonstrates that pre-surgical serum lipid levels are linked to the clinical outcome of different types of human malignant tumors, but few studies have explored the prognostic value of these easily accessible parameters in glioblastoma. The aim of the current study was to validate the association between pre-surgical serum lipid levels and the clinical outcome of patients with glioblastoma. The pre-surgical serum lipid levels (triglycerides, total cholesterol, high-density lipoprotein [HDL] cholesterol, and low-density lipoprotein [LDL] cholesterol) of 125 patients with glioblastoma, who underwent surgery between January 2015 and May 2016, were retrospectively evaluated. The correlation between pre-surgical serum lipid levels and overall survival (OS) was examined using the Kaplan-Meier method and Cox proportional hazards regression model. Univariate analysis showed that lipids associated with OS were total cholesterol, HDL cholesterol, and LDL cholesterol levels. Results of multivariate analysis identified LDL cholesterol level as an independent prognostic factor for OS in patients with glioblastoma (hazard ratio: 0.412; 95% confidence interval: 0.211-0.801; P = 0.009). Total cholesterol and HDL cholesterol levels were predictive factors only in univariate analysis, but not in multivariate analysis. The current study demonstrated that pre-surgical serum LDL cholesterol level is an independent prognostic factor for clinical outcomes of patients with glioblastoma. Pre-surgical serum LDL cholesterol level might provide valuable prognostic information for patients with glioblastoma that could be applied in clinical practice.

show abstract

Preoperative statin use is not associated with improvement in survival after glioblastoma surgery

Cited by 22 publications

References 19 publications

MYC-Regulated Mevalonate Metabolism Maintains Brain Tumor–Initiating Cells

MYC-Regulated Mevalonate Metabolism Maintains Brain Tumor–Initiating Cells

Combined Treatment with Dopamine Receptor Antagonists and Radiation Creates a Metabolic Vulnerability in Mouse Models of Glioblastoma

Clinical significance of pre-surgical serum lipid levels in patients with glioblastoma

Contact Info

Product

Resources

About