Cannabinoids, commonly used for medicinal and recreational purposes, consist of various complex hydrophobic molecules obtained from Cannabis sativa L. Acting as an inhibitory molecule; they have been investigated for their antineoplastic effect in various breast tumor models. Lately, it was found that cannabinoid treatment not only stimulates autophagy-mediated apoptotic death of tumor cells through unfolded protein response (UPR ER ) activated downstream effectors, but also imposes cell cycle arrest. The exploitation of UPR ER tumors as such is believed to be a major molecular event and is therefore employed in understanding the development and progression of breast tumor. Simultaneously, the data on clinical trials following administration of cannabinoid is currently being explored to find its role not only in palliation but also in the treatment of breast cancer. The present study summarizes new achievements in understanding the extent of therapeutic progress and highlights recent developments in cannabinoid biology towards achieving a better cure of breast cancer through the exploitation of different cannabinoids.
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Peer review under responsibility of King Saud University.
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Cannabinoid therapies are particularly promising for tumor-producing cancers given that “no overtly cannabis-resistant tumors have been described so far,” according to the Spanish researchers. “Considering how different cancer subtypes are, and the fact that the viability of non-transformed cells is not affected by cannabinoids at the concentrations they kill tumor cells, it is tempting to speculate that these compounds tackle essential, as yet unidentified, cellular functions that all cancer cells share, and that are absent in their non-cancerous counterparts.”
Their findings were reported in a 2018 article – “Appraising the ‘Entourage Effect’: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer” – which was published in the journal Biochemical Pharmacology. The phrase “entourage effect” in this context refers to the full-spectrum synergistic interplay between numerous cannabis compounds – cannabinoids, terpenes and flavonoids – that impart a therapeutic impact that’s greater than the sum of the plant’s individual components.
Two biomarkers frequently used to diagnose breast cancer are hormonal receptors (the estrogen receptor and progesterone receptor) and the HER2 oncogene (a gene which can transform a normal cell into a tumor cell). But a more aggressive malignancy, known as “triple-negative breast cancer,” doesn’t express hormonal receptors or the HER2 oncogene. No targeted therapy exists for triple-negative breast cancer, so patients are treated with harsh chemotherapies that indiscriminately kill proliferating cells, whether cancerous or not.
CB2 actually conjoins with HER2 – forming what is called a dimer – and this dimerization is associated with poor treatment outcome for breast cancer. The PNAS report shed new light on THC ’s anticancer mechanism of action: When THC binds to the CB2 receptor, it breaks up the CB2 – HER2 dimer, triggering a chain reaction of signals that culminates in tumor regression.
It is estimated that one in eight women will develop breast cancer. Breast cancer is tricky to treat because there are few biomarkers that signal when someone has the disease, and many patients show or develop resistance to current therapies. Moreover, several specific types of breast cancer respond poorly to modern treatment. These difficulties underscore the importance of exploring new treatments for breast cancer.
There are several other examples where a combination of plant cannabinoids and standard chemotherapy agents have produced a heightened antitumoral response that exceeded the potency of either therapy alone. A phase 2 clinical trial tested the strength of Sativex, an equal THC and CBD mixture, combined with temozolomide, the “gold-standard” chemo for brain cancer, and the results were positive.
The Spanish breast cancer study underscores the importance of the entourage effect by demonstrating that full spectrum artisanal cannabis oil extract with numerous components is more effective than pure THC .* “[A]lthough the pharmacology of cannabis drug preparation extracts is obviously more complex to study,” the researchers acknowledge, “this therapeutic approach has the potential to produce better therapeutic responses than pure cannabinoids.”
Your doctor may not be enthusiastic about you using CBD, but that doesn’t necessarily mean they’re resistant to the idea. “Remember that your doctor wants to help manage your symptoms and pain, so being open and honest about what you need is the best way to communicate,” Weiss advises.
If you’re having breast cancer treatment side effects or symptoms that aren’t being controlled, or if you think your doctor isn’t listening to your needs or doesn’t have the experience to give you advice on CBD products, get a second opinion, Weiss suggests. She recommends talking to an oncologist who is knowledgeable about cannabis products if your doctor can’t help.
Side Effects and Risks
Your body has a natural endocannabinoid system, “a complex network of receptors on cells that regulates your daily body functions, such as inflammation, mood, and sleep,” says Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org and director of breast radiation oncology at Lankenau Medical Center in Wynnewood, PA.
Before she had a double mastectomy, reconstruction surgery, chemotherapy, and radiation for breast cancer in 2015, Mathias Schmucki says, she wouldn’t have put much stock in something like CBD (though she would have supported her patients’ choice to use it). But ibuprofen wasn’t relieving the itchy, scratchy, painful sensations she was having. She was so uncomfortable, “I was open to anything.” She knew that she didn’t need or want the mind-altering effects THC can create, so she decided to try CBD oil.
Andrea Mathias Schmucki, MD, patient advocate, Living Beyond Breast Cancer Hear My Voice advocacy program.