Phase II study of atorvastatin in combination with radiotherapy and temozolomide In patients with glioblastoma (ART): interim analysis report

Altwairgi, Abdullah; Alghareeb, Waleed; Alnajjar, Fouad; Alsaeed, Eyad; Balbaid, Ali Abdullah O; AlHussain, Hussain; Aldanan, S.; Orz, Yasser; Lari, A.; Alsharm, Abdullah

doi:10.1093/annonc/mdw367.32

Cited by 7 publications

(10 citation statements)

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“…Consistent with this, laboratory studies and a single case–control study have suggested a protective effect of statins on the risk of glioma which also suggests the potentially beneficial long-term use of statin to increase life expectancy in glioma patients 1 42. A phase II clinical trial has evaluated the synergistic effects of statins (atorvastatin) in combination with radiotherapy and TMZ in patients with GBM with promising results 8. However, the benefit of statins in combination treatments warrants further studies to explore and validate the use of statins in GBM 40…”

Section: Statins and Gbm Cancer Therapymentioning

confidence: 99%

Statins: A New Approach to Combat Temozolomide Chemoresistance in Glioblastoma

Shojaei

Alizadeh

Thliveris

et al. 2018

Journal of Investigative Medicine

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Patients with glioblastoma multiforme (GBM) have an average life expectancy of approximately 15 months. Recently, statins have emerged as a potential adjuvant cancer therapy due to their ability to inhibit cell proliferation and induce apoptosis in many types of cancer. The exact mechanisms that mediate the inhibitory actions of statins in cancer cells are largely unknown. The purpose of this proceeding paper is to discuss some of the known anticancer effects of statins, while focusing on GBM therapy that includes adjunct therapy of statins with chemotherapeutic agents.

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Section: Statins and Gbm Cancer Therapymentioning

confidence: 99%

Statins: A New Approach to Combat Temozolomide Chemoresistance in Glioblastoma

Shojaei

Alizadeh

Thliveris

et al. 2018

Journal of Investigative Medicine

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“…[27] Furthermore, combination therapy of temozolomide and ATV in combination with radiotherapy in newly diagnosed GBM patients was promising (progression free survival (PFS) rate at 6 months: 67 % and median PFS of 9.1 months), meeting criteria for continued accrual in a phase II clinical study (NCT02029573). [28] In addition, considerable evidence suggests that statins also exhibit immunomodulatory properties, [18] as e.g.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Blood-Brain-Barrier Permeability and Cytotoxicity of Atorvastatin-Loaded Nanoformulation Against Glioblastoma in 2D and 3D Models

Lübtow¹,

Oertner²,

Quader³

et al. 2019

Preprint

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Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase of the family of statins have been suggested as therapeutic options in various tumors. Atorvastatin is a statin with potential to cross the blood-brain-barrier, however, the concentrations necessary for a cytotoxic effect against cancer cells exceeds the concentration achievable via oral administration, which made the development of a novel atorvastatin formulation necessary. We characterized the drug loading and basic physicochemical characteristics of micellar atorvastatin formulations and tested their cytotoxicity against a panel of different glioblastoma cell lines. In addition, activity against tumor spheroids formed from mouse glioma and mouse cancer stem cells, respectively, was evaluated. Our results show good activity of atorvastatin against all tested cell lines. Interestingly, in the 3D models, growth inhibition was more pronounced for the micellar formulation compared to free atorvastatin. Finally, atorvastatin penetration across a blood-brain-barrier model obtained from human induced-pluripotent stem cells was evaluated. Our results suggest that the presented micelles may enable much higher serum concentrations than possible by oral administration, however, if transport across the blood-brain-barrier is sufficient to reach therapeutic atorvastatin concentration for the treatment of glioblastoma via intravenous administration remains unclear.<br>

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“…Agents that force the degradation of LDLR and block cholesterol uptake slow the growth of GBM cells in vitro and tumors in vivo. Systemic inhibition of LDLR may have a limited therapeutic window as genetic deletion of this target causes severe hypercholesterolemia and pharmacologic modulation appears to cause neuropsychiatric side effects [112,113]. The de novo synthesis of cholesterol is governed by the activity of hydroxylmethylglutaryl-CoA reductase (HMG-CoA reductase), which is inhibited by the statin drug class.…”

Section: Metabolic Characteristics Of Idhwtgbmmentioning

confidence: 99%

“…Drugs in the statin class have anti-proliferative effects when used alone or in combination with DNA damaging agents in patient-derived GBM cell lines, but the mechanism accounting for this efficacy is uncertain [115]. Similar combination therapies are now being tested in the clinic in a small phase 2 trial, but final results have not yet been published [113].…”

Section: Metabolic Characteristics Of Idhwtgbmmentioning

confidence: 99%

Metabolic Abnormalities in Glioblastoma and Metabolic Strategies to Overcome Treatment Resistance

Zhou

Wahl

2019

Cancers

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Glioblastoma (GBM) is the most common and aggressive primary brain tumor and is nearly universally fatal. Targeted therapy and immunotherapy have had limited success in GBM, leaving surgery, alkylating chemotherapy and ionizing radiation as the standards of care. Like most cancers, GBMs rewire metabolism to fuel survival, proliferation, and invasion. Emerging evidence suggests that this metabolic reprogramming also mediates resistance to the standard-of-care therapies used to treat GBM. In this review, we discuss the noteworthy metabolic features of GBM, the key pathways that reshape tumor metabolism, and how inhibiting abnormal metabolism may be able to overcome the inherent resistance of GBM to radiation and chemotherapy.

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Phase II study of atorvastatin in combination with radiotherapy and temozolomide In patients with glioblastoma (ART): interim analysis report

Cited by 7 publications

References 0 publications

Statins: A New Approach to Combat Temozolomide Chemoresistance in Glioblastoma

Statins: A New Approach to Combat Temozolomide Chemoresistance in Glioblastoma

In Vitro Blood-Brain-Barrier Permeability and Cytotoxicity of Atorvastatin-Loaded Nanoformulation Against Glioblastoma in 2D and 3D Models

Metabolic Abnormalities in Glioblastoma and Metabolic Strategies to Overcome Treatment Resistance

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