Seminars

Breastcanceris not a single disease, it is comprised of many biologically differentfeatures with distinct pathological and clinicalimplications. Accumulating evidence suggest breast cancers with different histopathological andbiological features exhibit different behaviors that lead to differenttreatment responses, and should be handled by different therapeutic strategies.In ERa-positivetumors, adjustive endocrine therapy, such as tamoxifen (TAM), is the standardfor a 5 years course.  However, almosthalf of the patients that start tamoxifen therapy do not complete the wholecourse. Poor adherence to tamoxifen has been associated with many reasonsincluding severe side effects such as hot flashes, pain and bleeding. In cancertreatment, Cannabisis being primarily used as palliative care to alleviate pain, relieve nauseaand stimulate appetite. However, asidefrom these palliative actions, extensive preclinical research demonstratedthat phytocannabinoids, theunique active components of the Cannabisplant, can trigger an antitumor response in different cancer models. Inthis study, we found a unique Cannabisstrain (CANN14) that has a synergistic effect with TAM on ERa-positivebreast cancer cells. CANN14 sensitizes the cells to TAM’s effect, allowing fora lower TAM concentration. Moreover, we isolated the phytocannabinoidsresponsible for the effect: THC, CBN and the novel phytocannabinoid331-18b. In a xenograft model, tumor growth was suppressed significantly withthe combined synergistic effect of TAM and CANN14. A combination of THC, CBNand 331-18b  in the same concentrationsas in CANN14 had a similar effect to the whole CANN14 on breast cancer cells.Furthermore, a higher concentration of 331-18b significantly sensitized thecells to lower TAM concentration by itself. The mechanism of breast cancer celldeath following exposure to CANN14 or the three pure cannabinoids involves areduction in ERaexpression and translation, as well as in its activity as a transcriptionfactor. These findings will allow, in thefuture, to make a compatible match between the Cannabisstrain and specific breast cancer tumor features. As a result, treatment dosagewill decrease and the patients’ quality of life will improve.