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The Pharmacogenomics of Opioid Response in Cancer Pain: From Receptor Polymorphisms to Tumour-Mediated Interference-A

Sebastiano Mercadante1

  • 1Main Regional of Supportive/Palliative Care, La Maddalena Cancer Center, Via San Lorenzo 312, 90146 Palermo, Italy.

International Journal of Molecular Sciences
|August 13, 2026
PubMed

Insights

Cancer pain treatment with opioids is highly variable. Genetic variations (polymorphisms) in opioid-related genes show promise for personalized medicine, but evidence is fragmented, and tumors complicate genotype-phenotype links.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Pain Management

Background:

  • Opioid therapy is central to cancer pain management but exhibits significant inter-individual variability.
  • Pharmacogenomics aims to explain this variability by studying genetic polymorphisms in opioid-related genes.
  • Despite extensive research, clinical application of pharmacogenomics for opioid prescribing in cancer pain remains limited.

Purpose of the Study:

  • To critically review the evidence on genetic polymorphisms influencing opioid response in cancer pain.
  • To examine pharmacodynamic, pharmacokinetic, and transporter gene categories relevant to opioid action.
  • To assess the impact of the tumor microenvironment on opioid pharmacogenomics.

Main Methods:

  • A narrative-critical literature review was performed using PubMed, Scopus, and Web of Science databases.
  • Search terms included "opioid," "pharmacogenomics," "cancer pain," and specific gene names.
  • Inclusion criteria prioritized studies on genetic polymorphisms and opioid response in cancer pain populations, with consultation of clinical guidelines.

Main Results:

  • Evidence on genetic polymorphisms affecting opioid response in cancer pain is poor and fragmented.
  • Numerous polymorphisms exist with context-dependent biological activity, complicating clinical translation.
  • The tumor microenvironment significantly interferes with genotype-phenotype relationships in opioid pharmacogenomics.

Conclusions:

  • Current evidence is insufficient for widespread clinical implementation of pharmacogenomics in cancer pain management.
  • The complexity of genetic variations and tumor-specific factors necessitates advanced research approaches.
  • A shift towards systems pharmacogenomics and multi-omic integration is required for future progress.
Keywords:
ABCB1COMTCYP2D6OPRM1SLC22A1SNPcancer paininterindividual variabilitymembrane transportersopioidspharmacogenomicsprecision medicinetumour microenvironment

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