Breast cancer is the most frequently diagnosed cancer worldwide, with over a million new cases diagnosed each year in the U.S. alone (Siegel, Cancer statistics, 2018). Although cases of breast cancer are often discussed in aggregate, breast cancer is quite heterogeneous, both at the molecular level and in terms of clinical outcomes.
Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer. Women with TNBC have significantly reduced survival compared to women with other forms of breast cancer for every tumor stage at presentation (Bauer, Cancer, 2007). Because targeted therapies do not exist for TNBCs, the mainstays of therapy include surgery, radiotherapy, and chemotherapy. Traditional chemotherapy is often met with rapid resistance and consequently poor response rates (Yu, Clin Canc Res, 2013). Additional therapeutic avenues are desperately needed to combat this aggressive form of breast cancer.
CBD as an Adjunct to Standard of Care Treatment
Accumulating evidence suggests a potential role for cannabidiol (CBD) in the management of certain cancers. CBD is an attractive candidate for translation into clinical practice due the absence of psychoactive effects. Furthermore, it has been suggested that of several naturally occurring cannabinoids, including THC, CBD is the most potent inhibitor of cancer cell growth with minimal effects in healthy cells (Ligresti, J Pharm Exp Ther, 2006). In some rare instances, THC has also been demonstrated to increase tumor size, growth, and metastases for unclear reasons (McKallip, J Immunol, 2005).
Dr. Wai Liu discusses the potential merits of cannabinoids in breast cancer.
The mechanism by which CBD exerts its anti-tumor effects is not fully understood, although results from preclinical studies suggest they may be multifactorial. In the case of TNBC, CBD was shown to reduce cell viability of TNBC cell lines by dampening signaling pathways implicated in the development of cancer and through induction of programmed cell death (Shrivastava, Mol Cancer Ther, 2011; Elbaz, Mol Onc, 2015).
CBD substantially reduced tumor growth in mouse models of TNBC (Elbaz, Mol Onc, 2015; McAlister, Mol Canc Ther, 2011; Murase, Br J Pharmacol, 2014). Furthermore, CBD may incite damage in cells through the overproduction of unstable oxygen molecules, termed reactive oxygen species, that can damage other nearby molecules, such as nucleic acids, proteins, and lipids (Shrivastava, Mol Cancer Ther, 2011).
CBD was also shown to impact other critical aspects of cancer. In mouse models of TNBC, CBD substantially reduced metastases, perhaps due to the downregulation of a key regulator of tumor metastasis, ID-1 (McAlister, Mol Cancer Ther, 2007; McAlister, Mol Canc Ther, 2011; Murase, Br J Pharmacol, 2014).
Additionally, in order for tumors to persist, grow, and invade locally, tumor cells must degrade the surrounding extracellular matrix and develop new blood vessels to support the growth. In CBD-treated mice with TNBC, there was significant downregulation of enzymes known to degrade the extracellular matrix and decreased recruitment of tumor-associated macrophages (TAMs) (Elbaz, Mol Onc, 2015), which are known to secrete growth factors that support the development of new blood vessels and secrete enzymes that support local tissue invasion (Condeelis, Cell, 2006).
Taken together, CBD was shown to influence several key processes in cancer pathogenesis including tumor growth, local invasion, and metastasis, and further research is warranted.