Molecular pathways: beta-adrenergic signaling in cancer.
Title | Molecular pathways: beta-adrenergic signaling in cancer. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Cole SW, Sood AK |
Journal | Clin Cancer Res |
Volume | 18 |
Issue | 5 |
Pagination | 1201-6 |
Date Published | 2012 Mar 1 |
ISSN | 1078-0432 |
Keywords | Adrenergic beta-Antagonists, Animals, Antineoplastic Agents, Clinical Trials as Topic, Humans, Neoplasms, Receptors, Adrenergic, beta, Signal Transduction, Translational Medical Research |
Abstract | 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. |
DOI | 10.1158/1078-0432.CCR-11-0641 |
Alternate Journal | Clin. Cancer Res. |
PubMed ID | 22186256 |
PubMed Central ID | PMC3294063 |
Grant List | CA109298 / CA / NCI NIH HHS / United States CA116778 / CA / NCI NIH HHS / United States R01 CA109298 / CA / NCI NIH HHS / United States R01 CA109298-08 / CA / NCI NIH HHS / United States R01 CA116778 / CA / NCI NIH HHS / United States R01 CA116778-05 / CA / NCI NIH HHS / United States |