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HER2 Positive Breast Cancer

Branna Z.
woman's shirt with pink ribbon on it

HER2 positive proteins can form a compound with CB2 receptors that increases the deadliness of breast cancer. THC may stop that from happening.

Breast cancer is complex disease with numerous molecular markers, multiple treatments,  and variant prognoses. Recently, treatments have progressed to the point that a tumor might be treatable that less than a decade ago would have been untreatable. Still, some treatments work better than others. Further, some cancer types are different than others. For example, there is a subtype of breast cancer that is characterized by the overexpression of the human epidermal growth factor 2 (HER2). It represents 15-20% of all breast tumors and patients with this expression are said to be HER2 positive.

What Does it Mean to be HER2 Positive?

HER2 positive cancers are cancers that grow by increasing the activity and number of proteins that control cell proliferation. Current HER2 breast cancer therapies work by targeting this overexpression of HER2. Thankfully, Trastuzumab, a recombinant humanized monoclonal anti-HER2 antibody, significantly improves outcome for patients.

However, despite its efficacy in many HER2 positive breast cancer cases, some patients do not respond to this treatment at all. Others eventually develop resistance to the drug. Therefore, doctors need an alternate treatment to address this growing problem in breast cancer patients.

women holding hands in pink shirts for breast cancer

Anti-Tumor Action of Cannabinoids

Cannabinoids produce anti-tumor responses in preclinical models of cancer, including HER2 positive breast cancer. In most cases, the anti-tumor responses are a result of the  binding and activating of cannabinoid receptors, CB1- and CB2 receptors. Preclinical research into HER2 positive tumors finds that CB2 is the main target for anti-tumor treatment.

A possible clue for the mechanism of turning HER2 on and off involves the formation of this double protein molecule, called a heterodimer. It forms between HER2 and CB2 receptor. Science does not yet understand the functional relevance of these heterodimers. However, some scientists believe that the higher the expression of the heterodimers (HER2-CB2R), the less favorable the patient outcome.

Research also found a higher expression of heterodimers in the metastatic tissue of the primary HER2 positive tumors.

Study Determines THC Can Target Heterodimers

A 2019 study was performed in vitro, analyzing several different HER2 positive breast cancer cell lines. Scientists know that CB2 receptor activation in models of HER2+ breast cancer causes cancer cell death. Scientists call the mechanism which leads to this is “apoptosis.” Apoptosis’ cell death inhibits tumor growth, tumor blood vessel formation, and tumor metastasis.

HER2 positive cell lines were treated with THC in order to test the hypothesis. The results showed that THC definitely decreased the viability of these cancer cell lines in a concentration dependent manner. THC treatment diminished the amount of CB2R that joined with HER2, which points to the cannabinoid-induced disruption of the heterodimer.

Data shows that THC decreases the volume of these heterodimer complexes by activating the CB2 receptors. The findings conclude that THC disrupts HER2-CB2R heterodimers. Further, it blocks HER2 activation, and then also promotes its degradation. All of this adds up to a significant anti-tumor response.

breast cancer woman in tank top checking for lumps

Showing A Potential New Mechanism For Anti-Tumor Treatments

To summarize, this study shows a mechanism controlling the activity of the HER2 that may represent a new target for anti-tumor treatments. Specifically, HER2 physically interacts with a membrane receptor (CB2) that doesn’t belong to the HER2 family. This interaction creates a CB2-HER2 heterodimer, which associates with poor outcomes for HER2 positive patients. THC inactivates this coupling process and degrades HER2, thus promoting anti-tumor action.

Its important to note that this is an in vitro study. This means that the researchers took cells of a particular type and exposed them to a certain type of cannabis. It does not mean that, say, consuming cannabis in an ordinary manner like smoking or edibles has any inherent anti-tumor activity. Therefore, it is possible that other cell types  could relate to this process. For example, immune cells, and endothelial cells, also express CB2 receptors. Therefore, it is reasonable to think that THC might also affect them. It would be interesting to see if the preclinical data could support the results demonstrated in this study.

Ultimately, this is an exciting time to be a patient. More and more changes are making cancer more and more survivable. Soon a day may come when cannabis medicine is involved in those changes.

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Branislava Zagorac
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