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Heterogeneity in hormone-dependent breast cancer and therapy: Steroid hormones, HER2, melanoma antigens, and cannabinoid receptors

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Breast cancer is the most frequently diagnosed cancer and the leading cause of death by cancer among women worldwide. The prognosis of the disease and patients’ response to different types of therapies varies in different subgroups of this heterogeneous disease. The subgroups are based on histological and molecular characteristics of the tumor, especially the expression of estrogen (ER) and progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Hormone-dependent breast cancer, determined predominantly by the presence of ER, is the most common type of breast cancer. Patients with hormone-dependent breast cancer have an available targeted therapy, however, tumor cells can develop resistance to the therapy, which is a major obstacle limiting the success of treatment and enabling relapse to metastatic disease. …

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The potential for medicinal cannabis to help manage challenging behaviour in people with intellectual disability: A perspective review

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Around 2% of the population have intellectual disabilities. Over one-third people with intellectual disabilities (PwID) present with ‘challenging behaviour’, which nosologically and diagnostically is an abstract concept. Challenging behaviour is influenced by a range of bio-psycho-social factors in a population, which is unable to suitably comprehend and/or communicate concerns. This predisposes to poor health and social outcomes. There is no evidence-based treatments for managing challenging behaviour. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are being trialled for a range of disorders, which are over-represented in PwID and provoke challenging behaviours, such as severe epilepsy, spasticity, post-traumatic stress disorder, social phobia, pain, etc.

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FAAH inhibition ameliorates breast cancer in a murine model

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Breast cancer is the leading cancer among females worldwide. Disease outcome depends on the hormonal status of the cancer and whether or not it is metastatic, but there is a need for more efficacious therapeutic strategies where first line treatment fails. In this study, Fatty Acid Amide Hydrolase (FAAH) inhibition and endocannabinoids were examined as therapeutic alternatives. FAAH is an integral membrane enzyme that hydrolyzes endocannabinoids, rendering them inactive, and FAAH inhibition is predicted to increase cancer cell death. To test this, breast cancer cells were probed for FAAH expression using Western blot analysis, treated with FAAH inhibitors, exogenous endocannabinoids, and combinations of the two treatments, and assessed for viability.

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Anti-proliferative effect of Cannabidiol in Prostate cancer cell PC3 is mediated by apoptotic cell death, NFκB activation, increased oxidative stress, and lower reduced glutathione status

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Prostate cancer is the second most frequent cancer diagnosed in men in the world today. Almost all prostate cancers are adenocarcinomas and develop from gland cells. We used the PC3 prostate cancer cell line, which is well studied and derived from a bone metastasis of a grade IV prostatic adenocarcinoma. Cannabidiol (CBD), a major non-psychoactive constituent of cannabis, is a cannabinoid with anti-tumor properties but its effects on prostate cancer cells are not studied in detail. Here, we found cannabidiol decreased prostate cancer cell (PC3) viability up to 37.25% and induced apoptotic cell death in a time and dose-dependent manner. We found that CBD activated the caspases 3/7 pathways and increased DNA fragmentation. Furthermore, we observed an increase of pro-apoptotic genes Bax, an increased level of reactive oxygen species, lower reduced glutathione level, and altered mitochondrial potential in response to CBD treatment leading to lower cellular ATP. Overall, our results suggest that CBD may be effective against prostate cancer cells.

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Heterogeneity in hormone-dependent breast cancer and therapy: Steroid hormones, HER2, melanoma antigens, and cannabinoid receptors

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Breast cancer is the most frequently diagnosed cancer and the leading cause of death by cancer among women worldwide. The prognosis of the disease and patients’ response to different types of therapies varies in different subgroups of this heterogeneous disease. The subgroups are based on histological and molecular characteristics of the tumor, especially the expression of estrogen (ER) and progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Hormone-dependent breast cancer, determined predominantly by the presence of ER, is the most common type of breast cancer. Patients with hormone-dependent breast cancer have an available targeted therapy, however, tumor cells can develop resistance to the therapy, which is a major obstacle limiting the success of treatment and enabling relapse to metastatic disease.

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Cannabinoids and hormone receptor-positive breast cancer treatment.

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Authors: Luka Dobovišek, Fran Krstanović, Simona Borštnar, Nataša Debeljak
Cancers, 25 February 2020
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Breast cancer (BC) is the most common cancer in women worldwide. Approximately 70-80% of BCs express estrogen receptors (ER), which predict the response to endocrine therapy (ET), and are therefore hormone receptor-positive (HR+). Endogenous cannabinoids together with cannabin…

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Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer.

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Authors: Sandra Blasco-Benito, Marta Seijo-Vila, Miriam Caro-Villalobos, Isabel Tundidor, et al
Biochemical Pharmacology, November 2018
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Breast cancer is the second leading cause of death among women. Although early diagnosis and development of new treatments have improved their prognosis, many patients present innate or acquired resistance to current therapies. New therapeutic approaches are therefore warrante…

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Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer.

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Authors: Clara Andradas, Sandra Blasco-Benito, Sonia Castillo-Lluva, Patricia Dillenburg-Pilla, et al
Oncotarget, 26 July 2016
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The orphan G protein-coupled receptor GPR55 has been directly or indirectly related to basic alterations that drive malignant growth: uncontrolled cancer cell proliferation, sustained angiogenesis, and cancer cell adhesion and migration. However, little is known about the invo…

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Role of cannabinoid receptor CB2 in HER2 pro-oncogenic signaling in breast cancer.

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Authors: Eduardo Pérez-Gómez, Clara Andradas, Sandra Blasco-Benito, María M. Caffarel, et al
Journal of the National Cancer Institute, 8 April 2015
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BACKGROUND: Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different cancer models. However, the biological role of these receptors in tumor physio-pathology is still unknown. METHODS: We analyzed CB2 cannabinoid receptor protein expressio…

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Anandamide inhibits breast tumor-induced angiogenesis.

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Authors: P. Picardi, E. Ciaglia, M. C. Proto, S. Pisanti
Translational Medicine, 8 April 2014
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Breast cancer is one of the most frequently diagnosed malignancies and a leading cause of cancer death in women. Great advances in the treatment of primary tumors have led to a significant increment in the overall survival rates, however recurrence and metastatic disease, the…

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Disease modification of breast cancer-induced bone remodeling by cannabinoid 2 receptor agonists.

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Authors: Alysia N. Lozano‐Ondoua, Katherine E. Hanlon, Ashley M. Symons‐Liguori, et al
Journal of Bone and Mineral Research, January 2013
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Most commonly originating from breast malignancies, metastatic bone cancer causes bone destruction and severe pain. Although novel chemotherapeutic agents have increased life expectancy, patients are experiencing higher incidences of fracture, pain, and drug-induced side effec…

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Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis.

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Authors: Sean D. McAllister, Ryuichi Murase, Rigel T. Christian, Darryl Lau, Anne J. Zielinski, et al
Breast Cancer Research and Treatment, August 2011
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Invasion and metastasis of aggressive breast cancer cells are the final and fatal steps during cancer progression. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Therefore, effective, targeted, and non-toxi…

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