A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

Guzmán, Manuel; Duarte, Menezes; Blázquez, Cristina; Ravina, J H; Rosa, M C de la; Galve‐Roperh, Ismael; Sánchez, Cristina; Velasco, Guillermo; González-Feria, Luis

doi:10.1038/sj.bjc.6603236

Cited by 301 publications

(231 citation statements)

References 26 publications

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“…strated a marked reduction in Ki67 staining within the tumor (66). This observation together with the very promising results observed in cell cultures and laboratory animals (8 -12) suggest that administering cannabinoids alone or in conjunction with existing chemotherapeutic agents may be a promising treatment strategy for aggressive cancers of various origins.…”

Section: Discussionmentioning

confidence: 57%

Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth

DeMorrow

Glaser

Francis

et al. 2007

Journal of Biological Chemistry

160

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Cholangiocarcinomas are devastating cancers of biliary origin with limited treatment options. Modulation of the endocannabinoid system is being targeted to develop possible therapeutic strategies for a number of cancers; therefore, we evaluated the effects of the two major endocannabinoids, anandamide and 2-arachidonylglycerol, on numerous cholangiocarcinoma cell lines. Although anandamide was antiproliferative and proapoptotic, 2-arachidonylglycerol stimulated cholangiocarcinoma cell growth. Specific inhibitors for each of the cannabinoid receptors did not prevent either of these effects nor did pretreatment with pertussis toxin, a G i/o protein inhibitor, suggesting that anandamide and 2-arachidonylglycerol did not exert their diametric effects through any known cannabinoid receptor or through any other G i/o protein-coupled receptor. Using the lipid raft disruptors methyl-␤-cyclodextrin and filipin, we demonstrated that anandamide, but not 2-arachidonylglycerol, requires lipid raft-mediated events to inhibit cellular proliferation. Closer inspection of the lipid raft structures within the cell membrane revealed that although anandamide treatment had no observable effect 2-arachidonylglycerol treatment effectively dissipated the lipid raft structures and caused the lipid raft-associated proteins lyn and flotillin-1 to disperse into the surrounding membrane. In addition, anandamide, but not 2-arachidonylglycerol, induced an accumulation of ceramide, which was required for anandamide-induced suppression of cell growth. Finally we demonstrated that anandamide and ceramide treatment of cholangiocarcinoma cells recruited Fas and Fas ligand into the lipid rafts, subsequently activating death receptor pathways. These findings suggest that modulation of the endocannabinoid system may be a target for the development of possible therapeutic strategies for the treatment of this devastating cancer.Cholangiocarcinomas are devastating cancers of intrahepatic and extrahepatic origin that are increasing in both their worldwide incidence and mortality rates (1, 2). The challenges posed by these often lethal biliary tract cancers are daunting; conventional treatment options are limited, and the only hope for long term survival is that of complete surgical resection of the tumor (1, 2). Conventional chemotherapy and radiation therapy are not effective in prolonging long term survival (1); therefore it is important to understand the cellular mechanisms of cholangiocarcinoma cell growth with a view to develop novel chemopreventive strategies.Marijuana and its derivatives have been used in medicine for many centuries, and presently there is an emerging renaissance in the study of the therapeutic effects of cannabinoids. Ongoing research is determining that regulation of the endocannabinoid system may be effective in the treatment of pain (3, 4), glaucoma (5), and neurodegenerative disorders such as Parkinson disease (6) and multiple sclerosis (7). In addition, cannabinoids might be effective antitumoral agents because of their abil...

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Section: Discussionmentioning

confidence: 57%

Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth

DeMorrow

Glaser

Francis

et al. 2007

Journal of Biological Chemistry

160

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“…Notably, not only in vitro cell culture systems are subject to this treatment response but also in vivo experiments using either xenografts or syngeneic mouse models have shown the potential of cannabinoids as anticancer agents, without observing major psychoactive or immune-suppressive effects (8,13). Recently, the first clinical study using Δ 9 -tetrahydrocannabinol (THC) in severe cases of glioblastoma has been reported (14).…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma

Oesch

Walter

Wachtel

et al. 2009

Molecular Cancer Therapeutics

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Gene expression profiling has revealed that the gene coding for cannabinoid receptor 1 (CB1) is highly up-regulated in rhabdomyosarcoma biopsies bearing the typical chromosomal translocations PAX3/FKHR or PAX7/FKHR. Because cannabinoid receptor agonists are capable of reducing proliferation and inducing apoptosis in diverse cancer cells such as glioma, breast cancer, and melanoma, we evaluated whether CB1 is a potential drug target in rhabdomyosarcoma. Our study shows that treatment with the cannabinoid receptor agonists HU210 and Δ 9 -tetrahydrocannabinol lowers the viability of translocationpositive rhabdomyosarcoma cells through the induction of apoptosis. This effect relies on inhibition of AKT signaling and induction of the stress-associated transcription factor p8 because small interfering RNA-mediated down-regulation of p8 rescued cell viability upon cannabinoid treatment. Finally, treatment of xenografts with HU210 led to a significant suppression of tumor growth in vivo. These results support the notion that cannabinoid receptor agonists could represent a novel targeted approach for treatment of translocation-positive rhabdomyosarcoma.

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“…24 Aside from one clinical trial with end-stage glioblastoma multiforme patients, THC has not been studied clinically as a treatment for malignancy. 8 Unfortunately, there are many claims on the internet about the "curative" effects THC can have for cancer patients, where these articles often cite ongoing research articles. However, these articles and websites extrapolate in vitro study results and preclinical work into humans without any basis in fact.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

“…1,[5][6][7] To date, there has only been one clinical trial looking at the antitumoural activity of cannabinoids on terminal human patients harbouring actively growing recurrent gliomas. 8 Hence, this review will outline the current evidence on the antiproliferative effects of endocannabinoids in the male genitourinary malignancies, including renal, prostate, bladder, and testicular cancers, and look to explore the possible role of future human clinical trials in the field.…”

Section: Introductionmentioning

confidence: 99%

Systematic review of the potential role of cannabinoids as antiproliferative agents for urological cancers

Gandhi

Vasisth

Kapoor

2017

CUAJ

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Introduction: The palliative effects of cannabis sativa (marijuana), which include appetite stimulation, attenuation of nausea and emesis, and pain relief, are well known. The active components of cannabis sativa (cannabinoids) and their derivatives have received growing interest due to their diverse pharmacological activities, such as cell growth inhibition and tumour regression. The aim of this review is to look at the current evidence on the antiproliferative effects of cannabinoids in urological malignancies, including renal, prostate, bladder, and testicular cancers. Methods: We conducted a systematic review of studies exploring the effect of cannabinoids on tumour activity, including all study types except expert opinions. A formal search was run on Medline database from 1946 to September 2016, along with a hand-search on PubMed for relevant studies. Results: The search yielded a total of 93 studies from Medline and PubMed, of which 23 studies were included in the final analysis. To date, there are various in vitro studies elucidating the potential mechanism of action of cannabinoids for urological cancers, along with population-based studies specifically for testicular malignancies. To date, no clinical trials have been conducted for urological cancer patients.Conclusions: These results demonstrate that the role of endocannabinoids for urological malignancies is an area of active research. Further research is required not only to evaluate the crosstalk between cancer signaling pathways and cannabinoids, but also large randomized clinical studies with urological patients need to be conducted before cannabinoids can be introduced as potential therapeutic options for urological neoplasms.

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A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

Cited by 301 publications

References 26 publications

Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth

Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth

Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma

Systematic review of the potential role of cannabinoids as antiproliferative agents for urological cancers

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