How THC May Disrupt Breast Cancer Metastasis

Dragana Komnenov PhD May 24, 2019 0 comments

In vivo studies show THC and breast cancer at odds.

The development of breast cancer has multiple triggers and therefore, varied outcomes for the patient. This type of cancer has specific subsets with distinct tumor shape and location. It affects prognosis and the recommended course of treatment. Collected data on common characteristics of the subsets of breast cancer gives opportunity for more relevant, personalized treatment. THC has shown great promise in stopping the mechanisms of tumor growth for HER2 and Triple Negative Breast Cancer (TNBC)

CB1 and CB2 Receptor Signaling Has Anti-Tumor Action

CB1 and CB2 receptor expression differs among the subtypes of breast cancer. For one quarter of breast cancer patients, there is an increase in CB1 receptors overall. This is most evident for HER2 tumors. Three quarters of breast cancers have an increase in CB2 receptors, most profoundly in HER2 and TNBC.

Lab researchers use WIN-55, a synthetic version of THC. It is important that initial phases of research use very specific doses and concentration of cannabinoids. This allows research teams to create ‘proof of principle’ so that things can move toward clinical trials.

WIN-55  was shown to significantly diminish the growth and metastasis in TNBC tumors. The suspected mode of action is through CB1 and/or CB2 activation. Additionally, both CBD and THC were shown, in two separate studies, to slow proliferation and metastasis of TNBC and HER2 positive tumors in mice.

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THC May Prevent Breast Cancer Taking Over UPR Mechanism

When breast tumors reach the status of metastasis, it means they have gained access to the bloodstream and lymphatic system. This increases mortality rates significantly. Tumor cells get busy making more of themselves, amping up their little cellular machinery to very high levels. These levels typically exceed the ability of the cells to deal with all the newly synthesized proteins. It’s exactly like a traffic jam that starts folding in on itself.

This jam causes considerable stress on the cell. The response of normal cells would be to send out a signal called the “Unfolded Protein Response” (UPR). The UPR has three jobs to do: (1) Stop proteins from being made; (2) Destroy the extra proteins that are clogging up things; and (3) Activate the chaperone molecules to get in there and stop this nonsense. If there is a failure in any of these, the cell will go into apoptosis and die.

Breast cancer cells exploit this UPR mechanism with some cross talk and signalling to actually increase the demand for new proteins. Like that scene in I Love Lucy where Lucy gets a job at a chocolate factory only she can’t wrap the chocolates fast enough, so they start piling up. So, then she’s trying to eat them and shove them into her shirt, instead of turning off the belt. And by taking over this UPR mechanism, tumor cells achieve immortality.

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THC Gets The Traffic Flowing Again

Initial in vitro studies involving THC explored how THC stops cancer cells from continuing to grow. This reduces tumor proliferation. Interestingly, THC (in the lab) disrupted the protein pile up of the breast cancer cells. It accomplished this by activating CB2 receptors, which then activated autophagy. This is a housekeeping mechanism programmed into cells that starts the process of recycling proteins and cellular bits before going into apoptosis (cell death).

When cannabis gets on the scene, THC will initiate autophagy, which consists of multiple molecular signaling cascades and culminates in cell death. This decreases tumor cell proliferation.

What Does This Mean For Breast Cancer Patients?

So far, accumulating evidence points to the effectiveness of THC and CBD in HER2 and TNBC breast cancer cell lines. Studies in mouse models demonstrated that THC stops/slows tumor progression. New in vitro data has emerged, as described in this article, that UPR targeting could be an effective therapeutic strategy.  Future investigations must prove that THC targeting of UPR in vivo stops breast cancer progression.

Currently, cannabinoids are used for appetite stimulation, management of acute pain and as an anti-nauseants. It’s time to perform preclinical and clinical studies to find out if THC and breast cancer has therapeutic applicability of cannabinoids in designing treatments for breast cancer.