Opioids and cancer survival: are we looking in the wrong place?

There is a controversial narrative in the anaesthetic literature suggesting that anaesthetic technique (including opioids) may be detrimental to survival after tumour resection. The initial observations were retrospective. Several prospective studies are ongoing; one in breast cancer has reported no...

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Main Authors: Despina Giakomidi, Mark F. Bird, David G. Lambert
Format: Article
Language:English
Published: Elsevier 2022-06-01
Series:BJA Open
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2772609622000090
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author Despina Giakomidi
Mark F. Bird
David G. Lambert
author_facet Despina Giakomidi
Mark F. Bird
David G. Lambert
author_sort Despina Giakomidi
collection DOAJ
description There is a controversial narrative in the anaesthetic literature suggesting that anaesthetic technique (including opioids) may be detrimental to survival after tumour resection. The initial observations were retrospective. Several prospective studies are ongoing; one in breast cancer has reported no adverse outcome. The evidence for an effect of opioids stems from three pieces of information: (1) opioids depress the immune system, (2) opioids potentially promote angiogenesis, and (3) opioids potentially support tumour growth. Although the evidence for (2)/(3) is unclear, combinations of these effects are beneficial to tumours and potentially promote metastatic reseeding. Accepted wisdom suggests that opioid effects are driven by opioid receptor activation but the presence of opioid receptors on immune cells for example is unlikely. Immune cells, vascular endothelium and a range of tumour cells express Toll-like receptor 4 (TLR4) receptors (for Gram-negative bacterial wall components), and there is growing evidence for opioids interacting with this alternative receptor; and for some there is paradoxical naloxone sensitivity. Is the focus on opioid receptors and cancer the wrong target? TLR4 receptor activation produces immune activation, stimulates angiogenesis, and supports tumour survival. We know that some opioids are more immune suppressive than others (there is no such comparative information for angiogenesis and tumour survival); this may correlate with TLR4 activation. If there are clusters of opioids that have more opioid than TLR4 profiles and vice versa, this may influence outcome. If this is the case, then evidence-based advice could be given for perioperative use in the oncology–anaesthesia setting.
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spelling doaj.art-009c367cf2f14379aeae7c228d2532592022-12-22T03:49:02ZengElsevierBJA Open2772-60962022-06-012100010Opioids and cancer survival: are we looking in the wrong place?Despina Giakomidi0Mark F. Bird1David G. Lambert2Department of Cardiovascular Sciences (Anaesthesia, Critical Care and Pain Management), University of Leicester, Hodgkin Building, Leicester, UKDepartment of Cardiovascular Sciences (Anaesthesia, Critical Care and Pain Management), University of Leicester, Hodgkin Building, Leicester, UKCorresponding author.; Department of Cardiovascular Sciences (Anaesthesia, Critical Care and Pain Management), University of Leicester, Hodgkin Building, Leicester, UKThere is a controversial narrative in the anaesthetic literature suggesting that anaesthetic technique (including opioids) may be detrimental to survival after tumour resection. The initial observations were retrospective. Several prospective studies are ongoing; one in breast cancer has reported no adverse outcome. The evidence for an effect of opioids stems from three pieces of information: (1) opioids depress the immune system, (2) opioids potentially promote angiogenesis, and (3) opioids potentially support tumour growth. Although the evidence for (2)/(3) is unclear, combinations of these effects are beneficial to tumours and potentially promote metastatic reseeding. Accepted wisdom suggests that opioid effects are driven by opioid receptor activation but the presence of opioid receptors on immune cells for example is unlikely. Immune cells, vascular endothelium and a range of tumour cells express Toll-like receptor 4 (TLR4) receptors (for Gram-negative bacterial wall components), and there is growing evidence for opioids interacting with this alternative receptor; and for some there is paradoxical naloxone sensitivity. Is the focus on opioid receptors and cancer the wrong target? TLR4 receptor activation produces immune activation, stimulates angiogenesis, and supports tumour survival. We know that some opioids are more immune suppressive than others (there is no such comparative information for angiogenesis and tumour survival); this may correlate with TLR4 activation. If there are clusters of opioids that have more opioid than TLR4 profiles and vice versa, this may influence outcome. If this is the case, then evidence-based advice could be given for perioperative use in the oncology–anaesthesia setting.http://www.sciencedirect.com/science/article/pii/S2772609622000090angiogenesiscancerimmune functionopioidsTLR4 receptors
spellingShingle Despina Giakomidi
Mark F. Bird
David G. Lambert
Opioids and cancer survival: are we looking in the wrong place?
BJA Open
angiogenesis
cancer
immune function
opioids
TLR4 receptors
title Opioids and cancer survival: are we looking in the wrong place?
title_full Opioids and cancer survival: are we looking in the wrong place?
title_fullStr Opioids and cancer survival: are we looking in the wrong place?
title_full_unstemmed Opioids and cancer survival: are we looking in the wrong place?
title_short Opioids and cancer survival: are we looking in the wrong place?
title_sort opioids and cancer survival are we looking in the wrong place
topic angiogenesis
cancer
immune function
opioids
TLR4 receptors
url http://www.sciencedirect.com/science/article/pii/S2772609622000090
work_keys_str_mv AT despinagiakomidi opioidsandcancersurvivalarewelookinginthewrongplace
AT markfbird opioidsandcancersurvivalarewelookinginthewrongplace
AT davidglambert opioidsandcancersurvivalarewelookinginthewrongplace