Propranolol: A “Pick and Roll” Team Player in Benign Tumors and Cancer Therapies

Abstract

Research on cancer therapies focuses on processes such as angiogenesis, cell signaling, stemness, metastasis, and drug resistance and inflammation, all of which are influenced by the cellular and molecular microenvironment of the tumor. Different strategies, such as antibodies, small chemicals, hormones, cytokines, and, recently, gene editing techniques, have been tested to reduce the malignancy and generate a harmful microenvironment for the tumor. Few therapeutic agents have shown benefits when administered alone, but a few more have demonstrated clear improvement when administered in combination with other therapeutic molecules. In 2008 (and for the first time in the clinic), the therapeutic benefits of the β-adrenergic receptor antagonist, propranolol, were described in benign tumors, such as infantile hemangioma. Propranolol, initially prescribed for high blood pressure, irregular heart rate, essential tremor, and anxiety, has shown, in the last decade, increasing evidence of its antitumoral properties in more than a dozen different types of cancer. Moreover, the use of propranolol in combination therapies with other drugs has shown synergistic antitumor effects. This review highlights the clinical trials in which propranolol is taking part as adjuvant therapy at single administration or in combinatorial human trials, arising as a good pick and roll partner in anticancer strategies.

Leveraging β‐Adrenergic Receptor Signaling Blockade for Improved Cancer Immunotherapy Through Biomimetic Nanovaccine

“…[20][21][22] Propranolol (Pro) is a nonselective β-AR inhibitor that has demonstrated clinical efficacy in hypertension, cardiac arrhythmias and myocardial infarction, and is now being used experimentally for cancer immunotherapy. [23,24] However, systematic administration of Pro might have the risk of side effects related to the central nervous and cardiovascular system (e.g., sleep disturbance, agitation, bronchospasm/bronchial hyperreactivity and hypoglycemia). [25] With these findings in mind, we propose to construct a nanocarrier that controllably delivers Pro to permit specific targeting to lymph nodes and TME for minimal systemic adverse effects with maximal immunomodulatory outcomes when combined with cancer vaccines.…”

An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma

“…We speculate this is due to suppression of the SOX18-MVP-axis in tumor endothelial cells and in turn, tumor angiogenesis. Propranolol is currently being studied as single administration adjuvant therapy or in combination with standard therapies in several clinical trials (57). Statin use was first found associated with improved outcomes in colorectal cancer patients in 2005 (58) and subsequent studies confirmed this observation and extend to post-diagnosis statin use (59–64).…”

Ranolazine: a potential anti-metastatic drug targeting voltage-gated sodium channels

“…This is a beta blocker which has been shown to have anti-cancer effects on various carcinomas [ 48 ]. Interestingly, it is also an effective blocker of neuronal and cardiac VGSCs [ 49 ].…”