Evaluation of natural and novel tumour-selective cannabinoids in melanoma progression and metastases

The majority of deaths from melanoma following conventional therapies are a result of metastases. A recent study suggests that the plant-derived, non-psychoactive cannabinoid, Cannabidiol (CBD), reduced the growth of melanoma cells in mice, but the effects of Cannabidiol (CBD) and other natural and synthetic cannabinoid on melanoma metastasis remains unknown. Our unpublished data confirm that natural cannabinoids such as CBD and our novel tumour-selective cannabis-like agents reduce the growth and motility of a panel of aggressive melanoma cells – thereby suggesting a therapeutic role for cannabinoids in the management of melanoma metastasis.

This project will build on these findings and our group previous work on the role of the endocannabinoid system in cancer associated bone disease, and will evaluate whether natural and novel tumour-selective synthetic cannabinoid agents affect the ability of melanoma cells to grow, move and influence the function of immune cells in the tumour microenvironment in vitro and ex vivo and in preclinical mouse models.

If successful, the findings of this research will have translational potential in identifying whether topical application of natural or synthetic cannabinoids - in combination with immunotherapy – are of value for the management of metastatic melanoma. Guided by these preclinical studies, we plan to conduct clinical trials to test the effects of CBD and an appropriate novel tumour-selective cannabinoid in advanced melanoma patients (in collaboration with Sarah J Danson, professor and Consultant of Medical Oncology, University of Sheffield).This addresses an unmet clinical need, as metastasis and acquired resistance to conventional anti-cancer therapy are clinical problems in advanced melanoma patients.