TMB and FGA Biomarkers Predict Anesthetic/Analgesic Immunomodulation Effects on Cancer Survival
Key Insights
Researchers found that tumor mutational burden (TMB) and fraction genome altered (FGA) can predict how anesthetic and analgesic drugs affect survival in cancer patients.
Increased TMB and FGA magnified opioid's pro-tumor effects in lung adenocarcinoma (search), while TMB reduced ketamine's anti-tumor effects.
In colon adenocarcinoma (search), increased TMB magnified opioid's anti-tumor effects on recurrence, suggesting a potential precision approach to oncoanalgesia.
The effects of anesthetic and analgesic drugs on cancer recurrence and survival may be predictable using tumor mutational burden (TMB) and fraction genome altered (FGA) biomarkers, according to a new study published in Frontiers in Anesthesiology. Researchers at Albert Einstein College of Medicine and Memorial Sloan Kettering Cancer Center investigated how these biomarkers interact with anesthetic/analgesic drugs to influence patient outcomes in lung and colon adenocarcinoma (search).
The study retrospectively analyzed two clinical cohorts of lung adenocarcinoma (search) (LUAD) and colon adenocarcinoma (search) (COAD) patients. Data from The Cancer Genome Atlas (TCGA), encompassing 6488 patients across 18 solid tumor types, was also examined. The researchers explored the relationship between anesthetic/analgesic drug exposure, TMB/FGA levels, and patient survival.
Key Findings
In LUAD patients, increased TMB and FGA were found to amplify the pro-tumor effects of opioids (search) on overall survival. Conversely, higher TMB levels diminished the anti-tumor effects of ketamine on recurrence. Ketorolac's anti-tumor effects on recurrence were not affected by TMB levels.
For COAD patients, increased TMB, indicative of DNA mismatch repair deficiency, enhanced the anti-tumor effects of opioids (search) on recurrence. The study also revealed correlations between drug target receptor gene expression, TMB, FGA, and tumor microenvironment (TME) immune cell types across various cancer types.
Implications for Precision Oncoanalgesia
These findings suggest that TMB and FGA could serve as predictive biomarkers for individual cancer patient responses to anesthetic/analgesic drugs, mediated through immunomodulation. The correlation between anesthetic/analgesic target receptor gene expression, TMB, FGA, and TME immune cell types points to potential molecular targets for further mechanistic studies.
"A precision oncoanalgesia approach in the cancer patient may ultimately be warranted to optimize oncological outcomes," the authors stated. This approach involves tailoring anesthetic and analgesic strategies based on a patient's unique genomic and immunological profile.
Future Directions
The researchers emphasize the need for further exploration of the molecular mechanisms underlying these interactions. By identifying specific drug target receptor genes and their relationship to TMB, FGA, and immune cell types, it may be possible to develop more targeted and effective oncoanalgesic strategies. This could lead to improved survival rates and reduced recurrence in cancer patients undergoing anesthesia and analgesia.