Opioid Receptor-Mediated and Non-Opioid Receptor-Mediated Roles of Opioids in Tumour Growth and Metastasis

Abstract

Opioids are administered to cancer patients in the period surrounding tumour excision, and in the management of cancer-associated pain. The effects of opioids on tumour growth and metastasis, and their consequences on disease outcome, continue to be the object of polarised, discrepant literature. It is becoming clear that opioids contribute a range of direct and indirect effects to the biology of solid tumours, to the anticancer immune response, inflammation, angiogenesis and importantly, to the tumour-promoting effects of pain. A common misconception in the literature is that the effect of opioid agonists equates the effect of the mu-opioid receptor, the major target of the analgesic effect of this class of drugs. We review the evidence on opioid receptor expression in cancer, opioid receptor polymorphisms and cancer outcome, the effect of opioid antagonists, especially the peripheral antagonist methylnaltrexone, and lastly, the evidence available of a role for opioids through non-opioid receptor mediated actions.

Solid Tumor Opioid Receptor Expression and Oncologic Outcomes: Analysis of the Cancer Genome Atlas and Genotype Tissue Expression Project

“…For instance, particular SNPs such as the A118G have been linked to reduced sensitivity to opioid medication in the patient suffering from chronic pain ( 36 , 37 ) and cancer ( 19 ) and even cancer recurrence in specific tumor types and populations ( 38 , 39 ), Also, TLR4 gene polymorphisms have also been studied and may play a role in proliferation and differentiation and multiple isoforms of receptor subtype resulting from alternative splicing of the pre-mRNA transcript have been identified albeit their functional role has yet to be clarified ( 40 ). Investigators are beginning to expand the horizon outside the genetic profile of opioid receptors and to include specific genetic alterations such as Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A) mutations ( 41 ), although the influence that specific influence of individual receptor isoforms is still a matter of debate ( 42 ).…”

Implementation of a peri‐operative pain‐management algorithm reduces the use of opioid analgesia following pelvic exenteration surgery

“…A detailed guide to achieving opioid containment in the peri-operative period has been published recently by the Faculty of Pain Medicine [45]. Opioid analgesic agents have an in vitro effect on the biology of solid tumours, such as colorectal cancer; however, the long-term effect of opioid administration on tumour recurrence and survival is not well demonstrated in vivo [46]. Both this cohort of 2017-2018 and the cohort described by Lim et al (2013Lim et al ( -2014 found that bone and nerve resection did not impact VNRS in the first 7 days following surgery [4].…”

Perioperative Immunosuppressive Factors during Cancer Surgery: An Updated Review

“…For decades, it has been known that opioids affect various aspects of anticancer immunity, in particular lymphocyte proliferation and function, including effects on cytokine production and cytotoxicity [98,99]. Opioid receptors are also expressed on the membrane of tumor cells, affecting their metabolism [100]. Interestingly, all these characteristics are related to effects that are dose-and opioid type-dependent.…”