Opioid receptors beyond pain control: The role in cancer pathology and the debated importance of their pharmacological modulation

Abstract

Stimulation of opioid receptors is widely used for relieving cancer pain in patients with advanced cancer. The expression of tissue opioid receptors varies depending on the types of cancer and it is regulated by several factors. This review provides a focused overview of the current evidence for the role of opioid receptors in modulating cancer progression, a discussion of the proposed underlying mechanisms and the pharmacological activity of opioid agonists and antagonists. Conflicting evidence from preclinical and clinical studies suggests the possible involvement of opioid receptor agonists in both the development and suppression of human cancer. Some retrospective clinical studies also show a possible detrimental effect on long-term patient outcomes. Among the opioid receptor agonists, morphine has been extensively studied in various cancer types. Moreover, various pathological processes of human cancer are affected by opioid receptor agonists, such as tumour growth, angiogenesis and immunosuppression. These findings highlight the functional value of opioid receptors in human cancer, and a potential double role of opioid receptor agonists and antagonists in human cancer treatment.

Keywords: Angiogenesis; Cancer; FENTANYL: N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide; Immunosuppression; METHYLNALTREXONE: (4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium-7-one; MORPHINE: (4R,4aR,7S,7aR,12bS)-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol; Metastasis; NALOXONE: (4R,4aS,7aR,12bS)-4a,9-dihydroxy-3-prop-2-enyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one; NALTREXONE: (4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one; Opioid receptors; Opioids; TAPENTADOL: 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol; TRAMADOL: (1R,2R)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexan-1-ol.