The multifaceted role of beta‐blockers in overcoming cancer progression and drug resistance: Extending beyond cardiovascular disorders

Beta‐blockers are commonly used medications that antagonize β‐adrenoceptors, reducing sympathetic nervous system activity. Emerging evidence suggests that beta‐blockers may also have anticancer effects and help overcome drug resistance in cancer treatment. This review summarizes the contribution of different isoforms of beta‐adrenoceptors in cancer progression, the current preclinical and clinical data on associations between beta‐blockers use and cancer outcomes, as well as their ability to enhance responses to chemotherapy and other standard therapies. We discuss proposed mechanisms, including effects on angiogenesis, metastasis, cancer stem cells, and apoptotic pathways. Overall, results from epidemiological studies and small clinical trials largely indicate the beneficial effects of beta‐blockers on cancer progression and drug resistance. However, larger randomized controlled trials are needed to firmly establish their clinical efficacy and optimal utilization as adjuvant agents in cancer therapy. Modulation of the Tumor Microenvironment by β‐Blockers: The tumor microenvironment is critical for cancer progression and therapeutic resistance. Cancer‐associated fibroblasts and epithelial‐to‐mesenchymal transition promote a supportive tumor stroma and invasion. Angiogenesis, mediated by vascular endothelial growth factor, allows nutrient and oxygen delivery. Meanwhile, cytokine signaling enables immune evasion. Beta‐blockers may reshape the tumor microenvironment by inhibiting angiogenesis, modifying immune cell infiltration and function, disrupting catecholaminergic niche signaling, and attenuating surgery‐induced immunosuppression. These effects highlight the potential of beta‐blockers to modulate the tumor microenvironment as a novel strategy to improve cancer therapy.