Manipulation of tumour- and host-derived endocannabinoids for the treatment of prostate cancer metastasis

The majority of deaths from prostate cancer following the failure of conventional therapies are a result of metastases. The endogenous cannabinoid system plays an important role in the regulation of tumorigenesis and metastasis. Our unpublished data show that highly metastatic cancer cells express key components of the endogenous cannabinoid systems, and therapeutic manipulation of these targets by tumour-selective cannabinoids is likely to be of value in the prevention and treatment of metastasis associated with advanced prostate cancer. The overall aim of this application is to investigate if and how manipulation of tumour- and/or host-derived endocannabinoids by our novel, tumour-selective cannabinoids or by administration of cannabis clinical extracts influences metastases in our unique humanized and syngeneic models of metastatic prostate cancer in which key components of the cannabinoid system have been silenced. If successful, the findings of this research will have translational potential in identifying tumour-selective cannabinoids - alone or in combination therapy with conventional cancer therapies - for the treatment of advanced prostate cancer. In the longer term, we intend to exploit this knowledge to develop new treatments for advanced cancer patients based on targeting the cannabinoid system in tumours, and design clinical trials, guided by these studies, to test the effects of novel tumour-selective cannabinoids for the treatment of metastases. Studies of the role that cannabinoids play in metastases are novel, and if successful, will (a) stimulate research and development of a safer cannabis-based therapy for the treatment of cancer, and (b) address a huge unmet clinical need, as metastasis is a major problem affecting prostate cancer patients.