Role of classical cannabinoid receptors in cancer-associated bone disease

Introduction

The endocannabinoid system has been implicated in the regulation of various aspects of cancer including primary tumor growth, early and late metastases, cachexia, and pain [ ]. Skeletal-related events and bone pain are major causes of cancer-related morbidity, reduced quality of life, and death in patients with advanced cancers of bone, breast, and prostate origins [ ]. Pharmacological and genetic manipulation of the classical cannabinoid receptor type 1 (CB1) and type 2 (CB2), orphan receptor GPR55, and other related receptors such as vanilloid receptors affect bone remodeling in preclinical models of estrogen deficiency, arthritis, and age-related bone diseases [ , ]. In recent years, an increasing number of studies have implicated the endocannabinoid system and related systems in the initiation and progression of cancer-associated bone disease. Modulation of cannabinoid receptors and enzymes by pharmacological and molecular biology approaches have been found to affect all aspects of bone remodeling and pain in animal models of primary bone cancer and bone metastasis ( Fig. 23.1 ) [ , , , ]. The forthcoming sections review these studies, and argue the notion that administration of natural and/or synthetic cannabinoid ligands is of value in the management of skeletal and nonskeletal complications associated with metastatic cancer.