We are informing interested public that first cannabinoid formulation for treatment of hormone-positive breast cancer has been developed by International Institute for Cannabinoids ICANNA. It is intended for “add on” treatment and not for wider use without medical supervision. The development of the formulation was co-financed by the Slovene Enterprise Fund.
Breast cancer is the most common cancer in women in the developed world and therefore also an important public health problem. In Slovenia, the incidence of breast cancer is increasing and today more than 1,200 women fall ill every year, which is about five times more than in 1961.
Source: http://www.slora.si/documents/11561/20218/Dojka.pdf
There has been great progress in the treatment of breast cancer in recent decades, and the mortality rate has declined significantly since the late 1990s, mainly due to adjuvant systemic biologic therapy and early detection. Below are the scientific grounds of the formulation, which are intended primarily for the medical profession and patients who would like to better understand the action of cannabinoids on various cancer subtypes.
Scientific grounds of the cannabinoid formulation
Despite progress in cancer treatment, certain subtypes of breast cancer still do not respond well to oncology therapies. The term “breast cancer” encompasses a group of diseases that each have different molecular profiles and are treated with different therapies and have different clinical outcomes. Cancer cells can strongly express specific biomarkers, the hormone receptors estrogen (ER) and progesterone (PR), or the growth factor receptor – HER2R, or they do not express any of them. These markers are both prognostic and predictive factors. Based on the expression of these biological markers, breast tumors are divided into three subtypes.
Estrogen receptor positive (ER +) or progesterone receptor positive (PR +)
In about two out of three cases, breast cancer (more common in older women) has receptors for one or both hormones. Patients with ER + / PR + respond well to treatment with a combination of phytocannabinoids CBD and THC. Cannabinoids have been found to stop the cell cycle, thereby preventing cancer cells from dividing. Cannabinoids effectively inhibit the migration of ER + / PR + cancer cells, thereby modulating the metastasis of hormone-sensitive breast cancer. In patients with ER + (including triple positive), THC should be used with caution, because some studies have shown that high levels of THC can stimulate the growth of hormone-positive tumors, so for patients with hormone-positive cancer, treatment with predominantly CBD is most appropriate. (to a lesser extent with THC).
HER2 positive (Human Epidemal Growth Factor Receptor 2 or human epidermal growth factor 2 receptor)
HER2 is a human epidermal growth factor 2 receptor that is overexpressed on the cell surface, making tumor cell proliferation faster. HER2-positive cancers spread faster than others and are more invasive. Today, biological drugs are available in the form of monoclonal antibodies that successfully block this over-expressed receptor. The prognosis for patients with HER2 + has improved significantly with the introduction of biologic antibody therapy. Preclinical studies suggest that cannabinoids may also be useful here as adjuvant therapy. THC showed significant antitumor activity and not only reduced tumor growth but also their spread (metastasis). The vascularity of the tumor has also decreased, which further inhibits its growth. Combinations with a higher THC content are also suitable for this subtype of breast cancer.
Triple negative breast cancer
In this type of tumor, the malignant cells express neither hormone receptors nor HER2 receptors, so it is called triple negative. This type of breast cancer is spreading aggressively and the combination of chemotherapeutics is the only effective treatment. A wide range of synthetic cannabinoids was tested in cell models of this subtype and the effects observed ranged from inhibition of cell proliferation, increased apoptosis, to significantly reduced tumor growth and vascularity. Despite the positive results, due to various factors, these cannabinoids are not (yet) useful as medicines. There is a long way from laboratory to approved medicine. Synthetic cannabinoids, despite their limitations for research, are very useful for elucidating the mechanisms of the antitumor effect of cannabinoids. Interestingly, some of the antitumor effects are mediated through the CB1 receptor, but most of them through the CB2 receptor. The best anti-tumor effects were achieved by activating both cannabinoid receptors. This again points to the benefits of whole plant extracts that contain a range of active ingredients and can activate both receptors.
Use of cannabinoids and terpenes in breast cancer
Preclinical studies suggest that cannabinoids may be useful as an adjunct treatment for all three subtypes of breast cancer, and their therapeutic potential is most demonstrated in HER2-positive and triple-negative breast tumors. The therapeutic potential of cannabinoids is particularly important for women with the latter, as the prognosis for this subtype is generally poor, with the cannabinoid combination not only having to be adapted to the breast cancer subtype but also individually for each patient following her response.
Cannabidiol or CBD
CBD was found to be suitable for all three subtypes of breast cancer. Its action is based on a combination of direct activation of TRPV1 receptors and poor or indirect activation of CB2 receptors, in addition to inhibiting the degradation of anandamide. CBD in malignantly altered cells also causes stress to the endoplasmic reticulum (ER), a tubular cell organelle that plays an important role in the maturation and directing of proteins in cells. ER-stress triggers autophagy and apoptosis and consequent tumor cell collapse. CBD also works at the level of gene expression, namely it reduces the expression of the promethastatic gene ID1 (inhibitor of DNA binding 1) in cancer cells, which leads to inhibition of cancer progression. CBD also inhibits FOXM1 (Forkhead box M1), which is a transcription factor involved in cell proliferation, while increasing the expression of GDF15 (growth differentiation factor 15), a cytokine associated with tissue differentiation.
Cannabigerol or CBG
Another plant cannabinoid, cannabigerol or CBG, is important in breast cancer because it activates CB2 receptors. It has also been proven that a particularly important and synergistic combination of CBD and CBG, or whole plant extracts containing both cannabinoids. CBG also triggers all antitumor effects also through activation of the TRPM8 receptor.
Delta-9-tetrahydrocannabinol or THC
It is a cannabinoid that is responsible for the psychoactive action of cannabis and has a unique spectrum of effects. It binds to both CB1 and CB2 receptors, and has a number of other molecular targets in addition to these. Its antitumor activity has been demonstrated in many cancer models and encompasses several mechanisms of action, from triggering autophagy to inhibiting metastasis and neovascularization. In breast cancer, the action of this cannabinoid is specific, especially in hormone-positive cancer, as some studies suggest that it can act on the estrogen receptor and lower the antitumor immune response and promote tumor growth. This evidence is not unequivocal, as some studies point in another direction as well, but because we are looking for the most optimal scientifically unambiguously validated formulation, THC is not implemented here.
Limonene
Which terpenes and in what quantity they are found in hemp depends very much on the chemovar (“strain”) as well as on the growing conditions and the method of processing the plant. Like cannabinoids, terpenes are present mostly in the flower of the plant (trichomes), and only to some degree in the leaves. Terpene, which plays a particularly important role in breast cancer, is limonene. Limonene is present in many cannabis chemovars in significant quantities. It has been shown to trigger apoptosis of breast cancer cells. Research with preoperative patients showed that limonene caused cell cycle arrest in breast tissue, resulting in decreased tumor growth.
Conclusion
For patients with breast cancer, whole plant extracts rich in CBD and CBG are suitable as add-on therapy, and the benefits of whole plant extracts are multifaceted. Terpenes are also becoming increasingly important in the treatment of various diseases. Their individual effects are well studied and have medical potential, and terpenes in particular are important in combination with cannabinoids as they affect their binding to cannabinoid receptors.
It is important to note that the use of cannabinoids in combination with oncology treatment may be synergistic if cannabinoid-based drugs are added to oncology drugs. The latter increase the effect of drugs or enable the same effect with a reduced dose of a classic drug, which consequently reduces side effects (this does not apply to all oncology drugs). Cannabinoid cancer treatment cannot and should not replace standard combination therapy (surgery, systemic therapy, radiation).
For more information about the formulation please contact us at cannabinoid-clinic@institut-icanna.com.
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