The endocannabinoid system may play a dual role on the regulation of tumor generation and progression.
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Administration of THC and other cannabinoids exert anticancer actions in animal models of cancer.
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THC and other cannabinoid receptor-ligands induce cancer cell death and inhibit tumor angiogenesis.
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Cannabinoids enhance the anticancer activity of other antineoplastic agents in animal models of cancer.
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Cannabinoids are currently being tested as anticancer agents in phase I/II clinical studies.
Abstract
It is well-established that cannabinoids exert palliative effects on some cancer-associated symptoms. In addition evidences obtained during the last fifteen years support that these compounds can reduce tumor growth in animal models of cancer. Cannabinoids have been shown to activate an ER-stress related pathway that leads to the stimulation of autophagy-mediated cancer cell death. In addition, cannabinoids inhibit tumor angiogenesis and decrease cancer cell migration. The mechanisms of resistance to cannabinoid anticancer action as well as the possible strategies to develop cannabinoid-based combinational therapies to fight cancer have also started to be explored. In this review we will summarize these observations (that have already helped to set the bases for the development of the first clinical studies to investigate the potential clinical benefit of using cannabinoids in anticancer therapies) and will discuss the possible future avenues of research in this area.
Abbreviations
2-AG
2-arachidonoylglycerol
ALK
anaplastic lymphoma kinase
ATF-4
activating transcription factor 4
CB1
cannabinoid CB1 receptor
CB2
cannabinoid CB2 receptor
CBD
cannabidiol
CHOP
C/EBP homologous protein
EGFR
epidermal growth factor receptor
ER
endoplasmic reticulum
ERK
extracellular signal-regulated kinase
MDK
midkine
mTORC1
mammalian target of rapamycin complex 1
THC
Δ9-tetrahydrocannabinol
TRIB3
tribbles-homologue 3
TRPV1
transient receptor potential cation channel subfamily V member 1 (TRPV1)