Category Archives: Cancer

Targeting GPCRs Against Cardiotoxicity Induced by Anticancer Treatments.

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Image result for frontiers in cardiovascular medicine“Novel anticancer medicines, including targeted therapies and immune checkpoint inhibitors, have greatly improved the management of cancers. However, both conventional and new anticancer treatments induce cardiac adverse effects, which remain a critical issue in clinic.

Cardiotoxicity induced by anti-cancer treatments compromise vasospastic and thromboembolic ischemia, dysrhythmia, hypertension, myocarditis, and cardiac dysfunction that can result in heart failure. Importantly, none of the strategies to prevent cardiotoxicity from anticancer therapies is completely safe and satisfactory.

Certain clinically used cardioprotective drugs can even contribute to cancer induction. Since G protein coupled receptors (GPCRs) are target of forty percent of clinically used drugs, here we discuss the newly identified cardioprotective agents that bind GPCRs of adrenalin, adenosine, melatonin, ghrelin, galanin, apelin, prokineticin and cannabidiol.

We hope to provoke further drug development studies considering these GPCRs as potential targets to be translated to treatment of human heart failure induced by anticancer drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/32039239

https://www.frontiersin.org/articles/10.3389/fcvm.2019.00194/full

“Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis.”  https://www.ncbi.nlm.nih.gov/pubmed/25569804

Cannabinoid Signaling in Glioma Cells.

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 “Cannabinoids are a group of structurally heterogeneous but pharmacologically related compounds, including plant-derived cannabinoids, synthetic substances and endogenous cannabinoids, such as anandamide and 2-arachidonoylglycerol.

Cannabinoids elicit a wide range of central and peripheral effects mostly mediated through cannabinoid receptors. There are two types of specific Gi/o-protein-coupled receptors cloned so far, called CB1 and CB2, although an existence of additional cannabinoid-binding receptors has been suggested. CB1 and CB2 differ in their predicted amino acid sequence, tissue distribution, physiological role and signaling mechanisms.

Significant alterations of a balance in the cannabinoid system between the levels of endogenous ligands and their receptors occur during malignant transformation in various types of cancer, including gliomas.

Cannabinoids exert anti-proliferative action in tumor cells.

Induction of cell death by cannabinoid treatment relies on the generation of a pro-apoptotic sphingolipid ceramide and disruption of signaling pathways crucial for regulation of cellular proliferation, differentiation or apoptosis. Increased ceramide levels lead also to ER-stress and autophagy in drug-treated glioblastoma cells.

Beyond blocking of tumor cells proliferation cannabinoids inhibit invasiveness, angiogenesis and the stem cell-like properties of glioma cells, showing profound activity in the complex tumor microenvironment. Advances in translational research on cannabinoid signaling led to clinical investigations on the use of cannabinoids in treatments of glioblastomas.”

https://www.ncbi.nlm.nih.gov/pubmed/32034716

https://link.springer.com/chapter/10.1007%2F978-3-030-30651-9_11

“Cannabinoids exert anti-proliferative action in tumor cells.” https://www.ncbi.nlm.nih.gov/pubmed/22879071

“A glioma is a primary brain tumor that originates from the supportive cells of the brain, called glial cells.” http://neurosurgery.ucla.edu/body.cfm?id=159

“Remarkably, cannabinoids kill glioma cells selectively and can protect non-transformed glial cells from death.” http://www.ncbi.nlm.nih.gov/pubmed/15275820

The Highs and Lows of Cannabis in Cancer Treatment and Bone Marrow Transplantation.

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 Logo of rmmj“In the last decade, we have observed an increased public and scientific interest in the clinical applications of medical cannabis.

Currently, the application of cannabinoids in cancer patients is mainly due to their analgesic and anti-emetic effects.

The direct effects of phyto-cannabinoids on cancer cells are under intensive research, and the data remain somewhat inconsistent. Although anti-proliferative properties were observed in vitro, conclusive data from animal models and clinical trials are lacking.

Since immunotherapy of malignant diseases and bone marrow transplantation are integral approaches in hemato-oncology, the immuno-modulatory characteristic of cannabinoids is a fundamental aspect for consideration. The effect of cannabinoids on the immune system is presently under investigation, and some evidence for its immuno-regulatory properties has been shown.

In addition, the interaction of cannabinoids and classical cytotoxic agents is a subject for further investigation. Here we discuss the current knowledge of cannabinoid-based treatments in preclinical models and the limited data in oncological patients. Particularly, we address the possible contradiction between the direct anti-tumor and the immune-modulatory effects of cannabinoids.

Better understanding of the mechanism of cannabinoids influence is essential to design therapies that will allow cannabinoids to be incorporated into the clinic.”

https://www.ncbi.nlm.nih.gov/pubmed/32017682

Treatment with Cannabinoids as a Promising Approach for Impairing Fibroblast Activation and Prostate Cancer Progression.

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ijms-logo “Endo-, phyto- and synthetic cannabinoids have been proposed as promising anti-cancer agents able to impair cancer cells’ behavior without affecting their non-transformed counterparts.

However, cancer outcome depends not only on cancer cells’ activity, but also on the stromal cells, which coevolve with cancer cells to sustain tumor progression.

Here, we show for the first time that cannabinoid treatment impairs the activation and the reactivity of cancer-associated fibroblasts (CAFs), the most represented stromal component of prostate tumor microenvironment.

Overall, our data strongly support the use of cannabinoids as anti-tumor agents in prostate cancer, since they are able to simultaneously strike both cancer and stromal cells.”

https://www.ncbi.nlm.nih.gov/pubmed/31991773

https://www.mdpi.com/1422-0067/21/3/787

The Endocannabinoid System: A Target for Cancer Treatment.

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ijms-logo“In recent years, the endocannabinoid system has received great interest as a potential therapeutic target in numerous pathological conditions.

Cannabinoids have shown an anticancer potential by modulating several pathways involved in cell growth, differentiation, migration, and angiogenesis.

However, the therapeutic efficacy of cannabinoids is limited to the treatment of chemotherapy-induced symptoms or cancer pain, but their use as anticancer drugs in chemotherapeutic protocols requires further investigation.

In this paper, we reviewed the role of cannabinoids in the modulation of signaling mechanisms implicated in tumor progression.”

https://www.ncbi.nlm.nih.gov/pubmed/31979368

https://www.mdpi.com/1422-0067/21/3/747

“In addition to the symptomatic therapy of cancer patients, the antitumor effects of cannabinoids (whether in monotherapy or in combination with other cancer therapies) have promising potential in the treatment of cancer patients.”   https://www.ncbi.nlm.nih.gov/pubmed/31950844
“In addition to the well-known palliative effects of cannabinoids on some cancer-associated symptoms, a large body of evidence shows that these molecules can decrease tumour growth in animal models of cancer. In addition, cannabinoids inhibit angiogenesis and decrease metastasis in various tumour types in laboratory animals. Thus, numerous studies have provided evidence that thc and other cannabinoids exhibit antitumour effects in a wide array of animal models of cancer.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791144/


“Antitumour actions of cannabinoids.”   https://www.ncbi.nlm.nih.gov/pubmed/30019449 

“The endocannabinoid system as a target for the development of new drugs for cancer therapy” https://www.ncbi.nlm.nih.gov/pubmed/12723496

“Cannabinoids as Anticancer Drugs.”  https://www.ncbi.nlm.nih.gov/pubmed/28826542

http://www.thctotalhealthcare.com/category/cancer/

Cannabis use in pediatric cancer patients: what are they reading? A review of the online literature.

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“Recent changes to the legal status of marijuana in Canada warrant a review of the information that patients and families are accessing online regarding the role of cannabis in cancer.

The aims of the current research were to identify the quality of literature available online as well as the themes, and opinion (i.e., pro-, neutral, or anti-cannabis) of online articles.

RESULTS:

We found most articles were authored by journalists (39.4%) and MDs (14.1%) and published as news (35.2%) or web articles (28.2%). The content of articles focused on four themes: the reasons for and against cannabis use; the opinions of health care providers; the restrictions placed by governing bodies and the need for additional research, education, and standardization. Article opinions were neutral-pro-cannabis.

CONCLUSIONS:

Health care providers should be aware that the overall quality of information found online is considered “satisfactory.” The majority of articles present a pro-cannabis opinion.”

https://www.ncbi.nlm.nih.gov/pubmed/31960125

https://link.springer.com/article/10.1007%2Fs00520-020-05306-2

The role of cannabinoids in the treatment of cancer.

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“The aim of this review article is to summarize current knowledge about the role of cannabinoids and cannabinoid receptors in tumor disease modulation and to evaluate comprehensively the use of cannabinoids in cancer patients.

METHOD:

According to the PRISMA protocol, we have included data from a total of 105 articles.

RESULTS:

Cannabinoids affect cancer progression by three mechanisms. The most important mechanism is the stimulation of autophagy and affecting the signaling pathways leading to apoptosis. The most important mechanism of this process is the accumulation of ceramide. Cannabinoids also stimulate apoptosis by mechanisms independent of autophagy. Other mechanisms by which cannabinoids affect tumor growth are inhibition of tumor angiogenesis, invasiveness, metastasis, and the modulation of the anti-tumor immune response.

CONCLUSION:

In addition to the symptomatic therapy of cancer patients, the antitumor effects of cannabinoids (whether in monotherapy or in combination with other cancer therapies) have promising potential in the treatment of cancer patients. More clinical trials are needed to demonstrate the antitumor effect of cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/31950844

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Use of cannabinoids in cancer patients: A Society of Gynecologic Oncology (SGO) clinical practice statement.

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Gynecologic Oncology“Tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) affect the human endocannabinoid system.

Cannabinoids reduce chemotherapy induced nausea or vomiting (CINV) and neuropathic pain.

Each state has its own regulations for medical and recreational cannabis use.

Effects of cannabinoids on chemotherapy, immunotherapy, and tumor growth remain under investigation.

Providers should focus indications, alternatives, risks and benefits of medical cannabis use to make appropriate referrals.”

https://www.ncbi.nlm.nih.gov/pubmed/31932107

https://www.gynecologiconcology-online.net/article/S0090-8258(19)31805-0/fulltext

[Cannabidiol in cancer treatment].

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“Background: Cannabis was used for cancer patients as early as about 2500 years ago. Experimental studies demonstrated tumor-inhibiting activities of various cannabinoids more than 40 years ago. In view of the status of tetrahydrocannabinol (THC) as a regulated substance, non-psychotomimetic cannabidiol (CBD) is of particular importance.

Objectives: Efficacy of pure CBD in various animal models as well as initial results (case reports) from patients.

Methods: Review of the literature on animal experiments and observations in humans.

Results: Preclinical studies, particularly recent ones, including numerous animal models of tumors, unanimously suggest the therapeutic efficacy of CBD. In isolated combination studies, synergistic effects were generally observed. In addition, CBD may potentially play a role in the palliative care of patients, especially concerning symptoms such as pain, insomnia, anxiety, and depression. Further human studies are warranted.”

https://pubmed.ncbi.nlm.nih.gov/31897700

https://link.springer.com/article/10.1007/s00482-019-00438-9

Effect of combined doses of Δ9-tetrahydrocannabinol and cannabidiol or tetrahydrocannabinolic acid and cannabidiolic acid on acute nausea in male Sprague-Dawley rats.

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 “This study evaluated the potential of combined cannabis constituents to reduce nausea.

CONCLUSION:

Combinations of very low doses of CBD + THC or CBDA + THCA robustly reduce LiCl-induced conditioned gaping. Clinical trials are necessary to determine the efficacy of using single or combined cannabinoids as adjunct treatments with existing anti-emetic regimens to manage chemotherapy-induced nausea.”

https://www.ncbi.nlm.nih.gov/pubmed/31897571

https://link.springer.com/article/10.1007%2Fs00213-019-05428-4