The organ-specific modulation of malignant processes by opioids: a systematic review of cell culture studies

The International Agency for Research on Cancer (IARC) monographs recently classified opium consumption as carcinogenic to humans in certain organs, raising concerns regarding the effects of pharmaceutical opioids. This systematic review (Open Science Framework osf.io/xyg9p) evaluated whether opioid exposure causes organ-specific modulation of malignant processes in cancer cell culture studies.

We identified all research articles evaluating tumour modulation by opioids in vitro through 28/02/2024. Data on the organ of origin of cancer cells, opioid activity, opioid exposure, and cancer outcomes (tumour cell growth, metastasis, clonogenicity) were extracted. Statistical analyses were performed using Fisher's exact tests and multivariable logistic regression.

The anti-cancer outcome was the most prevalent (57%) while only 11% of experiments reported pro-cancer outcomes. A total of 230 publications, comprising 1465 experiments, were included. Low opioid concentrations (p = 0.0005), short exposure durations (p = 0.0035), and organs where cancer risk increases with opium use (p = 0.002), were associated with reporting of pro-cancer effects for opioid agonists.

The findings support a positive association between opioid exposure and growth of cancer cells from lung, bladder, larynx, pancreas, pharynx, stomach, or oesophagus and further reveal duration and concentration as critical factors in experiments evaluating the effects of opioids on cultured cancer cells.