Between 1970 and 1994, cancer claimed the lives of about 0.5 million Americans every year. According to the most recent statistics, it was estimated that approximately 1.3 million new cases of cancer would have been diagnosed and 555,500 people would have died from cancer in the United States in 2002. The development of therapeutic strategies for the prevention and treatment of cancer thus represents a key priority for the pharmaceutical industry (see "Cancer Treatment 2002" for a full analysis of current and future pharmaceutical approaches to cancer).

Angiogenesis represents an emerging therapeutic target which by 2006, is expected to command a market of $1.75 billion. Both stimulators and inhibitors of angiogenesis are being developed. Although inhibitors are primarily being developed for the treatment of cancer, these molecules are also receiving growing attention as a strategy for treating retinal diseases and also inflammatory conditions such as rheumatoid arthritis. The increase in interest in angiogenesis has been mirrored by a constantly expanding repertoire of molecular targets.

Cannabinoids and their derivatives exert their effects via "central" CB1 receptors, mostly expressed in brain and responsible for cannabinoid psychoactivity, and "peripheral" CB2 receptors, mostly expressed in the immune system and unrelated to cannabinoid psychoactivity. Cannabinoids may be potential antitumoral agents owing to their ability to induce the regression of various types of tumors, including lung adenocarcinoma, glioma, and thyroid epithelioma. Although cannabinoids directly induce apoptosis or cell cycle arrest in different transformed cells in vitro, the involvement of this and other potential mechanisms (e.g., inhibition of tumor angiogenesis) in their antitumoral action in vivo is as yet unknown. Researchers in Madrid have recently addressed this area using skin carcinoma as a model system. CB1 and CB2 receptors were identified on both neoplastic and non-neoplastic epidermal cells as well as human skin, keratinocytes, and carcinomas. Stimulation of these receptors using a mixed CB1/CB2 agonists caused apoptosis in transformed but not nontransformed epidermal cell lines or primary human keratinocytes. Furthermore, the CB2 agonist, was able to induce tumor regression in vivo. This effect was related to an increase in apoptosis and a decrease in angiogenesis, which in turn was related to an inhibition of EGF-R activation.

Skin cancer especially non-melanoma skin cancer is highly prevalent but also highly treatable especially if detected early. These data establish a proof of concept for the use of cannabinoid receptor agonists for the treatment of skin cancer. Perhaps of greater clinical interest however is the fact that these data also show for the first time that cannabinoid receptor activation is able to limit angiogenesis as well as induce apoptosis and further studies in other types of cancer are therefore eagerly awaited. Although a number of cannabinoid receptor agonists are in development few if any are currently being targeted towards the treatment of cancer. The ability of cannabinoids agonists to limit tumor progression as well as the anti-emetic properties of this therapeutic class supports further studies to investigate the therapeutic benefits of this pharmacological class.

Entry date February, 2003

Adapted from Casanova et al, J Clin Invest 2003 Jan;111(1):43-50 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk