Preclinical and Clinical Assessment of Cannabinoids as Anti-Cancer Agents

Abstract

Cancer is the second leading cause of death in the United States with 1.7 million new cases estimated to be diagnosed in 2016. This disease remains a formidable clinical challenge and represents a substantial financial burden to the US health care system. Therefore, research and development of novel therapeutics for the treatment of cancer is of high priority. Cannabinoids and their derivatives have been utilized for their medicinal and therapeutic properties throughout history. Cannabinoid activity is regulated by the endocannabinoid system (ECS), which is comprised of cannabinoid receptors, transporters, and enzymes involved in cannabinoid synthesis and breakdown. More recently, cannabinoids have gained special attention for their role in cancer cell proliferation and death. However, many studies investigated these effects using in vitro models which may not adequately mimic tumor growth and metastasis. As such, this article aims to review study results which evaluated effects of cannabinoids from plant, synthetic and endogenous origins on cancer development in preclinical animal models and to examine the current standing of cannabinoids that are being tested in human cancer patients.

Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration

“…CBR1, CBR2), and it is believed that signalling through this G-protein coupled receptor is required for CANN anticancer action. Most of the in vivo models of anticancer action of CANNs have focussed on cancers of the brain where there are high levels of CBR1, and a large proportion of these have indicated that CANN use is associated with decreased tumour growth and/or increased cell killing (6). These models have also shown the use of CANN can successfully support and enhance the action of other treatment modalities (7,8).…”

Synergistic interaction of the cannabinoid and death receptor systems – a potential target for future cancer therapies?

“…Current clinical studies mostly focus on patients with different types of glioblastoma, which are the most common and debilitating tumors of the CNS . These clinical results indicate that patients at least partially respond to cannabinoid treatments, and cellular and molecular examination of tissue samples indicates that the main reasons for the shrinkage of tumors appear to be the induction of autophagy and apoptosis and the decrease in vascularization of the tumor tissue . Though these studies are encouraging and further strengthen the potential use of cannabinoids in cancer therapy, further studies should be aimed at optimizing the use of cannabinoids in terms of patient selection based on genotyping or biomarker screening, or in combination with other anticancer agents such as recombinant DR ligands.…”

“…These drugs can increase appetite, reduce pain, and reduce chemotherapy‐associated nausea and vomiting. Many in vitro and in vivo studies also indicate that cannabinoid drugs can reduce tumor volume and induce cancer cell death . Both the CB1 and CB2 receptors, their endogenous ligands, and regulatory proteins are expressed, functionally active, and generally up‐regulated in most tumor cell lines .…”

“…Cannabinoid drugs make up one of the most promising classes of these drugs. Many studies have already focused on the co‐application of cannabinoids and other anticancer agents to sensitize a plethora of cancer cell lines in vitro . Some of these results are suggestive for CB and DR interaction; however, the data in some of these studies do not definitively demonstrate this connection, which remains a hypothesis .…”

“…Though these studies are encouraging, caution should be taken when these drugs are co‐administered in vivo . It should be taken into consideration that some cannabinoid drugs can promote cancer cell survival under certain conditions . The reason why certain cannabinoids support cancer cell survival while others efficiently kill cancer cells both in vitro and in in vivo models remains unclear.…”