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Transcriptomic Modulation of Inflammasome-Related Genes Following Metformin Administration in Breast Cancer Patients
Alireza Malayeri1, Mehdi Etemad Nezhad2, Farrokh Ramesh3
1Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Clinical Pharmacology : Advances and Applications
|June 11, 2026
Summary
Metformin treatment in breast cancer patients with paclitaxel-induced neuropathy altered inflammasome pathway gene expression. These transcriptomic changes suggest a potential role for metformin in managing chemotherapy-induced peripheral neuropathy (CIPN).
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of paclitaxel.
- The inflammasome complex (ASC, Caspase-1, NLRP3) plays a role in inflammatory pathways linked to neuropathy.
- Understanding transcriptomic changes in CIPN is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate transcriptomic alterations in inflammasome pathway genes in breast cancer patients undergoing paclitaxel therapy.
- To specifically evaluate the impact of metformin initiated after neuropathy onset on these gene expression levels.
Main Methods:
- A cohort of 51 breast cancer patients receiving paclitaxel were analyzed (26 controls, 25 metformin).
- Plasma samples were collected at multiple time points to quantify expression levels of ASC, Caspase-1, and NLRP3.
- Statistical analyses included temporal and group comparisons, correlation, and Receiver Operating Characteristic (ROC) analysis.
Main Results:
- Metformin treatment was associated with increased expression of ASC, Caspase-1, and NLRP3 in patients with neuropathy.
- ASC expression increased over time in the control group, but not Caspase-1 or NLRP3.
- ROC analysis showed moderate discriminatory ability for ASC and Caspase-1 in predicting outcomes.
Conclusions:
- Metformin administration post-neuropathy onset correlates with transcriptomic changes in inflammasome pathway genes.
- These findings suggest potential transcriptomic modulation by metformin, but not necessarily functional inflammasome activation.
- Further validation is needed due to limitations of plasma RNA reflecting cellular activity.
