Drug-associated pancreatic cancer: insights from real-world pharmacovigilance and network pharmacology.
Clinicians should be aware of potential pancreatic cancer risks associated with certain medications, especially in patients over 45 years of age.
Where it sits
this study against the rest of the goserelin corpusSummary and findings
This study aimed to identify drugs potentially associated with pancreatic cancer using the FDA Adverse Event Reporting System. A total of 33,948 reports were analyzed, revealing signals for 24 drugs, including GLP-1 analogues and DPP-4 inhibitors. The findings suggest a higher occurrence of pancreatic cancer in males over 45 years of age.
Abstract
<h4>Background</h4>Pancreatic cancer's high mortality rate necessitates our study, which aims to identify potential risk drugs and speculate on the underlying mechanisms.<h4>Research design and methods</h4>All pertinent reports from the FDA Adverse Event Reporting System database were extracted. The disproportionality analysis was used in signal detection and data on patient age, sex, weight, time to onset were collected. Seven databases were retrieved for network pharmacology. AutoDock Vina 1.1.2 was for molecular docking.<h4>Results</h4>Signals were detected among 397 drugs with pancreatic cancer report ≥3. Except 4 antineoplastic agents, only 24 drugs indicated pancreatic cancer signals in 33,948 reports including 4 dipeptidyl peptidase-4 (DPP-4) inhibitors, 3 glucagon-like peptide-1 (GLP-1) analogues, 5 compound hypoglycemic agents, 3 hypotensive agents, ranitidine, pancrelipase, fondaparinux, naldemedine, daprodustat, megestrol acetate, leuprorelin, lecanemab, and lorcaserin. Pancreatic cancer more occurred after the age of 45, with a higher proportion among male. Weight with GLP-1 analogues (median, 91 kg), and compound hypoglycemic agents (median, 82 kg) was heavier (<i>p</i> < 0.01). GLP1R (glucagon-like peptide 1 receptor) for GLP-1 analogues, and PTEN (phosphatase and tensin homolog) for metformin might be a potential cause of pancreatic cancer.<h4>Conclusion</h4>Clinicians providing these therapies should stay vigilant to detect pancreatic cancer early.
Background
Pancreatic cancer is known for its high mortality rate, prompting the need for studies that identify potential drug-related risks. Prior research has indicated various medications may be linked to increased cancer risk, but comprehensive analyses are limited. This study seeks to fill that gap by utilizing real-world pharmacovigilance data to explore associations between drugs and pancreatic cancer.
Methods
The study employed a disproportionality analysis of reports from the FDA Adverse Event Reporting System database. Data were collected on patient demographics, including age, sex, and weight. Seven databases were utilized for network pharmacology, and molecular docking was performed using AutoDock Vina 1.1.2. The analysis focused on identifying drugs with three or more reports of pancreatic cancer.
Results
Signals were detected among 397 drugs with pancreatic cancer report ≥3. A total of 24 drugs were identified as having signals in 33,948 reports. The study found that pancreatic cancer more frequently occurred in individuals over the age of 45, particularly among males. Statistical significance was noted with median weights for GLP-1 analogues and compound hypoglycemic agents, p < 0.01.
Interpretation
The findings suggest a potential association between certain drug classes and pancreatic cancer, aligning with previous literature that has raised concerns about specific medications. However, the effect sizes are not quantified in terms of clinical significance, and the observational nature of the study introduces confounding factors. The reliance on adverse event reports may limit the ability to establish a direct causal relationship, necessitating further investigation.
Key findings
- Signals were detected among 397 drugs with pancreatic cancer report ≥3.
- 24 drugs indicated pancreatic cancer signals in 33,948 reports.
- Median weight for GLP-1 analogues was 91 kg, and for compound hypoglycemic agents was 82 kg, p < 0.01.
- Pancreatic cancer more occurred after the age of 45, with a higher proportion among males.
Limitations
- Relies on adverse event reporting data, which may be subject to underreporting.
- Observational study design limits causal inferences.
- Potential bias in reporting due to the nature of pharmacovigilance data.