Molecular pathways: beta-adrenergic signaling in cancer.

TitleMolecular pathways: beta-adrenergic signaling in cancer.
Publication TypeJournal Article
Year of Publication2012
AuthorsCole, SW, Sood AK
JournalClinical cancer research : an official journal of the American Association for Cancer Research
Date Published2012 Mar 1
KeywordsAdrenergic beta-Antagonists, Animals, Antineoplastic Agents, Clinical Trials as Topic, Humans, Neoplasms, Receptors, Adrenergic, beta, Signal Transduction, Translational Medical Research

Beta-adrenergic signaling has been found to regulate multiple cellular processes that contribute to the initiation and progression of cancer, including inflammation, angiogenesis, apoptosis/anoikis, cell motility and trafficking, activation of tumor-associated viruses, DNA damage repair, cellular immune response, and epithelial-mesenchymal transition. In several experimental cancer models, activation of the sympathetic nervous system promotes the metastasis of solid epithelial tumors and the dissemination of hematopoietic malignancies via β-adrenoreceptor-mediated activation of protein kinase A and exchange protein activated by adenylyl cyclase signaling pathways. Within the tumor microenvironment, β-adrenergic receptors on tumor and stromal cells are activated by catecholamines from local sympathetic nerve fibers (norepinephrine) and circulating blood (epinephrine). Tumor-associated macrophages are emerging as key targets of β-adrenergic regulation in several cancer contexts. Sympathetic nervous system regulation of cancer cell biology and the tumor microenvironment has clarified the molecular basis for long-suspected relationships between stress and cancer progression, and now suggests a highly leveraged target for therapeutic intervention. Epidemiologic studies have linked the use of β-blockers to reduced rates of progression for several solid tumors, and preclinical pharmacologic and biomarker studies are now laying the groundwork for translation of β-blockade as a novel adjuvant to existing therapeutic strategies in clinical oncology.

Alternate JournalClin. Cancer Res.