Click to Enlarge: Beta adrenergic receptor signaling pathway. Legend: ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; PDE, phosphodiesterase; PKA, protein kinase A; Gαs, G-alpha subunit; Gβ/γ, G-beta/gamma subunits; β1, β2, β3, beta-adrenergic receptors. Source: MDPI Cancers
NEW YORK — Even though neural regulation contributes to pancreatic ductal adenocarcinoma (PDAC) development, the effects of neural-targeting medications on presentation or outcomes haven’t been well-documented according to a new study.
Four New York medical institutions—Columbia University Irving Medical Center, the Icahn School of Medicine at Mount Sinai and NYU Langone’s Laura and Isaac Perlmutter Cancer Center and the James J. Peters VAMC—sought to remedy that. The researchers conducted a retrospective study using the Veterans Affairs (VA) Corporate Data Warehouse (CDW) to identify patients with pancreatic cancer (2000-2020).
In the study, exposure to beta blocker, cholinergics or statins was defined by active prescriptions within 6 months before or 1 month after diagnosis. Defined as key outcomes were histologic subtype, stage, and overall survival (OS). Among 7,578 U.S. veterans with pancreatic cancer, 76% had adenocarcinoma, and 60% presented with stage IV disease.
The results, published in Cancer Epidemiology, Biomarkers & Prevention, indicate that beta blocker use was associated with lower odds of advanced stage (OR 0.55, 95% CI 0.5-0.63, p<0.0001) and improved overall survival (HR 0.89, 95%CI 0.84-0.95, p<0.0001). The authors report that cholinergic agonist use was associated with reduced likelihood of adenocarcinoma histology (OR 0.64, 95% CI 0.41-1.01, p=0.051) and advanced stage (OR 0.53, 95%CI 0.34-0.85, p=<0.0001), but not overall survival.1
Statin use, meanwhile,, was associated with higher likelihood of adenocarcinoma histology (OR 1.24, 95%CI 1.09-1.43, p=0.002) and lower odds of advanced stage (OR 0.77, 95%CI 0.68-0.88, p=<0.0001).
“Beta blockers were associated with earlier stage and improved survival,” the researchers conclude. “Cholinergic agonists and statins were associated with earlier stage. Cholinergic agonists were linked to lower likelihood of adenocarcinoma histology, while statins to higher likelihood. These findings suggest neural and metabolic pathways may shape early PDAC biology.”
They posit that autonomic and metabolic pathways might influence PDAC biology and suggest that beta blockers “merit mechanistic and clinical evaluation as adjunctive therapies.”
A study last year from the University of Toronto looked at the broader effects of beta blockers on cancer in general.
“Overall, this comprehensive meta-analysis found that beta blockade may be associated with longer PFS among patients with cancer, which was sustained after the exclusion of studies susceptible to ITB, [immortal time bias]” the Canadian authors wrote in Cancers (Basel). “There was a trend for BB use and longer CSS [cancer specific survival], but no difference observed for OS [overall survival] in the overall cohort; exploratory analyses by cancer type and stage were limited by small subgroup sizes.”2
The researchers added that beta blockers “currently represent a promising new avenue of adjunctive cancer therapy. In addition to their potential anti-cancer properties, BBs may also provide cardioprotective effects when used in patients receiving cardiotoxic systemic therapies.”
They suggested that high-quality evidence from large prospective and randomized studies, including ongoing phase II clinical trials, “will ultimately provide a more nuanced understanding of the association between beta blockade and outcomes in specific cancer patient populations and clinical contexts. If positive, these will confirm the utility of BBs as an accessible and cost-effective adjunct to existing cancer therapies.”
- Cham J, Yang E, Park J, White RA, Fojo T, Sigel K, Bates SE; Impact of Beta Blockers, Statins, and Cholinergic Agents on Clinical Outcomes in Pancreatic Cancer: A Retrospective VA Cohort Study. Cancer Epidemiol Biomarkers Prev 2026; https://doi.org/10.1158/1055-9965.EPI-26-0062
- Sharma AE, Chan S, Komorowski AS, Cao X, et. al. The Impact of Beta Blockers on Survival in Cancer Patients: A Systematic Review and Meta-Analysis. Cancers (Basel). 2025 Apr 18;17(8):1357. doi: 10.3390/cancers17081357. PMID: 40282534; PMCID: PMC12026060.
