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

Claudia A Scroope,Marie-Odile Parat,Markus W Hollmann,Zane Singleton

doi:10.3389/fonc.2021.792290

Claudia A Scroope, Marie-Odile Parat + Show 2 more

Open Access

https://doi.org/10.3389/fonc.2021.792290

Copy DOI

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.

Highlights

Opioids are administered to cancer patients to manage the pain associated with the disease, its treatment and in palliative care
We review the evidence on increased opioid receptor expression in tumours, the literature investigating opioid receptor polymorphisms and cancer outcome, and the effect of opioid antagonists, especially the peripheral antagonist methyl naltrexone (MNTX)
Of the six polymorphisms studied, the only one with a statistically significant impact on mortality was A118G Ten-year mortality was reduced in patients with at least one variant G allele at A118GBeing heterozygous for AG genotype was significantly protective over being homozygous for AA, with a reduced mortality rate of 9% compared to 18% GG genotype at A118G was uncommon in the studied population, precluding significant conclusions G allele presence is strongly associated with increased breast cancer incidence

Summary

Introduction

Opioids are administered to cancer patients to manage the pain associated with the disease, its treatment and in palliative care. The possibility that opioids may alter the course of cancer is of high clinical relevance. Opioids given to cancer surgery patients in the perioperative period are of particular interest because despite the short time frame when they are administered, they have been hypothesised to contribute, together with a number of other optimisable variables, to long-term cancer outcome [1, 2]. A systematic review and metaanalysis of the ability of analgesic drugs to reduce metastasis in experimental cancer models concluded that opioids did not show a significant effect on the incidence of metastasis [6]. Clinical studies have compared recurrence after cancer surgery employing regional anaesthesia and analgesia techniques, which allow pain control while reducing opioid exposure.

Methods

Results

Conclusion