Impact of cannabinoids on cancer outcomes in patients receiving immune checkpoint inhibitor immunotherapy

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 5, 2025

Cannabinoids relieve pain, nausea, anorexia and anxiety, improve quality of life in several cancer patients. The immunotherapy with checkpoint inhibitors (ICIs), although very successful a subset patients, is accompanied by moderate to severe immune-related adverse events (ir-AE) that often necessitate its discontinuation. Because their role symptomatic relief, cannabinoids have been used combination immune inhibitor (ICI) immunotherapy. A few studies strongly suggest the use medicinal cannabis patients attenuates many ir-AE associated ICI increase tolerability. However, no significant beneficial effects on overall survival, progression free survival or relapses were observed; rather, some noted concurrent administration clinical benefits latter. cannabinoids' well documented immunosuppressive mediated through cannabinoid recptor-2 (CB2), we propose considering this receptor as an inhibitory per se. simultaneous neutralization CB2, treatment, may lead better outcomes receiving In regard, such cannabidiol (CBD) cannabigerol (CBG), little agonism for be therapeutic choices. Additional strategies e.g., monoacylglycerol lipase (MAGL) degrade endocannabinoids lipogenesis formation lipid bilayers cells also explored. Future should take into consideration gut microbiota, CYP450 polymorphism haplotypes, cannabinoid-drug interactions genetic somatic variations occurring receptors signaling pathways personalized cannabis-based therapies ICIs. This rational knowledge-based regimens tailored individual

Language: Английский

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Rare Phytocannabinoids Exert Anti-Inflammatory Effects on Human Keratinocytes via the Endocannabinoid System and MAPK Signaling Pathway

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2721 - 2721

Published: Feb. 1, 2023

Increasing evidence supports the therapeutic potential of rare cannabis-derived phytocannabinoids (pCBs) in skin disorders such as atopic dermatitis, psoriasis, pruritus, and acne. However, molecular mechanisms biological action these pCBs remain poorly investigated. In this study, an experimental model inflamed human keratinocytes (HaCaT cells) was set up by using lipopolysaccharide (LPS) order to investigate anti-inflammatory effects cannabigerol (CBG), cannabichromene (CBC), Δ9-tetrahydrocannabivarin (THCV) cannabigerolic acid (CBGA). To aim, pro-inflammatory interleukins (IL)-1β, IL-8, IL-12, IL-31, tumor necrosis factor (TNF-β) IL-10 levels were measured through ELISA quantification. addition, IL-12 IL-31 after treatment HaCaT cells with THCV CBGA presence selected modulators endocannabinoid (eCB) signaling. latter cells, activation 17 distinct proteins along mitogen-activated protein kinase (MAPK) pathway also investigated via Human Phosphorylation Array. Our results demonstrate that significantly blocked inflammation reducing release all ILs tested, except for TNF-β. Moreover, reduction expression reverted blocking eCB-binding TRPV1 receptor inhibiting eCB-hydrolase MAGL. Remarkably, modulated phosphorylated forms (and hence activity) MAPK-related GSK3β, MEK1, MKK6 CREB engaging eCB hydrolases MAGL FAAH. Taken together, ability exert effect modifications MAPK signaling opens new perspectives inflammation-related pathologies.

Language: Английский

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Antitumor mechanism of cannabidiol hidden behind cancer hallmarks

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(4), P. 188905 - 188905

Published: May 8, 2023

Language: Английский

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Isobolographic interactions of cannabidiol and AM 1172 with cisplatin in human neuroblastoma and glioblastoma cell lines: an in vitro study

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111392 - 111392

Published: Jan. 1, 2025

Language: Английский

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New options for targeting TRPV1 receptors for cancer treatment: odorous Chinese herbal medicine

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 11, 2025

Vanilloid1 (TRPV1), a subfamily of transient receptor channels, is one the non-selective calcium which bridge between cellular response and extracellular environmental networks, involved in variety pathophysiological processes. It also process cancer occurrence progression, researchers are revealing its role cancer. In this paper, we review expression significance TRPV1 various cell types, apoptosis-proliferation balance, invasion metastasis, tumor micro-environment, with emphasis on mechanisms by mediates inflammatory response, immune system, thus regulates We discussed latest directions current challenges receptor-targeting therapy for cancer, summarized odorous traditional herbs that modulate receptors, view to developing anti-tumor drugs targeting receptors future.

Language: Английский

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The role of cannabinoid-mediated signaling pathways and mechanisms in brain disorders

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111653 - 111653

Published: Feb. 1, 2025

Language: Английский

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TRPM7 transactivates the FOSL1 gene through STAT3 and enhances glioma stemness

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(9)

Published: Aug. 29, 2023

We previously reported that TRPM7 regulates glioma cells' stemness through STAT3. In addition, we demonstrated FOSL1 is a response gene for TRPM7, and the serves as an oncogene to promote proliferation invasion.In present study, determined effects of on stem cell (GSC) markers CD133 ALDH1 by flow cytometry, maintenance activity extreme limiting dilution assays (ELDA). To further gain insight into mechanism which activates transcription contribute stemness, constructed promoter its GAS mutants followed luciferase reporter ChIP-qPCR in line patient-derived xenoline. examined GSC well immunohistochemistry staining (IHC) brain tissue microarray (TMA) patients.We revealed knockdown reduces expression ALDH1, required maintain cells. The experiments also showed mutations - 328 336 378 386 elements markedly reduced activity. Constitutively active STAT3 increased while dominant-negative decreased Furthermore, overexpression enhanced silencing STAT3, nuclear lysates cells stimulated constitutively activated can bind two elements, respectively. deacetylation at Lys-116 residue located within DNA binding domain led increase transcriptional found protein associated with grades malignant glioma, correlates patients.These combined results induced activation, mediated action shown be important stemness. These indicated FOSL1, similar diagnostic marker potential drug target patients.

Language: Английский

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Overcoming challenges in glioblastoma treatment: targeting infiltrating cancer cells and harnessing the tumor microenvironment

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Dec. 21, 2023

Glioblastoma (GB) is a highly malignant primary brain tumor with limited treatment options and poor prognosis. Despite current approaches, including surgical resection, radiation therapy, chemotherapy temozolomide (TMZ), GB remains mostly incurable due to its invasive growth pattern, drug penetration beyond the blood-brain barrier (BBB), resistance conventional therapies. One of main challenges in effectively eliminating infiltrating cancer cells that remain parenchyma after resection. We’ve reviewed most recent surveyed potential strategies aimed at enhancing local outcomes.

Language: Английский

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Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(9), P. 1245 - 1245

Published: Sept. 21, 2024

Background: Breast cancer therapy has been facing remarkable changes. Classic treatments are now combined with other therapies to improve efficacy and surpass resistance. Indeed, the emergence of resistance demands development novel therapeutic approaches. Due key estrogen signaling, receptor-positive (ER+) breast treatment always focused on aromatase inhibition ER modulation. Lately, effects phytocannabinoids, mainly Δ9-tetrahydrocannabinol (THC) cannabidiol (CBD), have evaluated in different cancers, including breast. However, Cannabis sativa contains more than 120 phytocannabinoids less researched understood. Methods: Here, we evaluated, both silico vitro, ability 129 modulate important molecular targets ER+ cancer: aromatase, ER, androgen receptor (AR). Results: In results suggested that some cannabinoids may inhibit act as ERα antagonists. Nine selected showed, potential either antagonists inverse agonist properties, or agonists. Moreover, these were considered weak inhibitors AR action. Conclusions: Overall, present, for first time, a comprehensive analysis actions tumors, pointing out their diseases.

Language: Английский

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New Avenues and Major Achievements in Phytocompounds Research for Glioblastoma Therapy

Molecules, Journal Year: 2024, Volume and Issue: 29(7), P. 1682 - 1682

Published: April 8, 2024

Phytocompounds have been evaluated for their anti-glioblastoma actions decades, with promising results from preclinical studies but only limited translation into clinics. Indeed, by targeting multiple signaling pathways deregulated in cancer, they often show high efficacy the vitro studies, poor bioavailability, low tumor accumulation, and rapid clearance compromise vivo. Here, we present new avenues phytocompound research improvement of glioblastoma therapy, including ways to enhance response temozolomide using phytochemicals, current focus on phytocompound-based immunotherapy, or use phytocompounds as photosensitizers photodynamic therapy. Moreover, new, intensively approaches, such chemical modifications phytochemicals encapsulation numerous types nanoformulations, improve bioavailability delivery brain. Finally, clinical trials evaluating role phytocompound-derived drugs therapy less studied plant extracts that recently found possess properties. Overall, recent advancements are encouraging; however, more 3D models, vivo it is possible upgrade treatment a satisfactory level.

Language: Английский

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