ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- A targetable opioid/cancer associated fibroblast axis drives extracellular matrix remodeling and tumor aggressiveness in pancreatic cancer.bioRxiv : the preprint server for biology · 2026Article
- Alprazolam Reduces Inflammatory Cytokine Production in Pancreatic Cancer-Associated Fibroblasts.Cancer research communications · 2026Article
- Lorazepam and Survival in Asian Patients with Pancreatic Cancer: A Retrospective Cohort Study.Journal of gastrointestinal cancer · 2026Article
- The impact of concomitant medications on treatment outcomes in patients with cancer receiving immune checkpoint inhibitors.Nature reviews. Cancer · 2026Review
- Pharmacological Activation of GPR68 Attenuates Ferroptosis in Spinal Cord Ischemia/Reperfusion Injury Through PI3K/Akt-Mediated Nrf2 Antioxidant Pathway.Inflammation · 2025Article
- Targeting Ion Channels for Cancer Therapy: From Pathophysiological Mechanisms to Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Mortality Risk of Colistin vs. Non-Colistin Use in Cancer Patients with Multidrug-Resistant Gram-Negative Bacterial Infections: Stratified by Resistance Profile and Concomitant Medications.Medicina (Kaunas, Lithuania) · 2025Article
- Long-term treatment with benzodiazepines and related Z-drugs exacerbates breast cancer: clinical evidence and molecular mechanisms.Cellular & molecular biology letters · 2025Article
- A real-world pharmacovigilance study of lorazepam based on the FDA adverse event reporting system database.Scientific reports · 2025Article
- Impact of Exposure to Benzodiazepines on Adverse Effects and Efficacy of PD-1/PD-L1 Blockade in Patients With Non-Small Cell Lung Cancer.Thoracic cancer · 2025Article
- Inhibition of GPR68 induces ferroptosis and radiosensitivity in diverse cancer cell types.Scientific reports · 2025Article
- Acid sensing to inflammaging: mechanisms and therapeutic promise of GPR68 (OGR1) in aging-related diseases.Frontiers in aging · 2025Review
- Concomitant exposure to benzodiazepines during pembrolizumab-based therapy for advanced non-small-cell lung cancer: a propensity-score matched analysis of monitoring agency data.Exploration of targeted anti-tumor therapy · 2025Article
- Elucidating the role of gut microbiota metabolites in diabetes by employing network pharmacology.Molecular medicine (Cambridge, Mass.) · 2024Article
- Article
- Review
- CAFs-Associated Genes (CAFGs) in Pancreatic Ductal Adenocarcinoma (PDAC) and Novel Therapeutic Strategy.International journal of molecular sciences · 2024Review
- Concomitant medication, comorbidity and survival in patients with breast cancer.Nature communications · 2024Article
- Recent advances in acid sensing by G protein coupled receptors.Pflugers Archiv : European journal of physiology · 2024Review
- GPR68-ATF4 signaling is a novel prosurvival pathway in glioblastoma activated by acidic extracellular microenvironment.Experimental hematology & oncology · 2024Article
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeThis research investigates the association between benzodiazepines (BZD) and cancer patient survival outcomes, the pancreatic cancer tumor microenvironment, and cancer-associated fibroblast (CAF) signaling. EXPERIMENTAL
designMultivariate Cox regression modeling was used to retrospectively measure associations between Roswell Park cancer patient survival outcomes and BZD prescription records. IHC, H&E, Masson's trichrome, RNAscope, and RNA sequencing were used to evaluate the impact of lorazepam (LOR) on the murine PDAC tumor microenvironment. ELISA and qPCR were used to determine the impact of BZDs on IL6 expression or secretion by human-immortalized pancreatic CAFs. PRESTO-Tango assays, reanalysis of PDAC single-cell sequencing/TCGA data sets, and GPR68 CRISPRi knockdown CAFs were used to determine the impact of BZDs on GPR68 signaling.
resultsLOR is associated with worse progression-free survival (PFS), whereas alprazolam (ALP) is associated with improved PFS, in pancreatic cancer patients receiving chemotherapy. LOR promotes desmoplasia (fibrosis and extracellular matrix protein deposition), inflammatory signaling, and ischemic necrosis. GPR68 is preferentially expressed on human PDAC CAFs, and n-unsubstituted BZDs, such as LOR, significantly increase IL6 expression and secretion in CAFs in a pH and GPR68-dependent manner. Conversely, ALP and other GPR68 n-substituted BZDs decrease IL6 in human CAFs in a pH and GPR68-independent manner. Across many cancer types, LOR is associated with worse survival outcomes relative to ALP and patients not receiving BZDs.
conclusionsWe demonstrate that LOR stimulates fibrosis and inflammatory signaling, promotes desmoplasia and ischemic necrosis, and is associated with decreased pancreatic cancer patient survival.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.