]> 2026-04-12T02:31:41-07:00 Beta-blockers (especially propranolol) and the role of the sympathetic 0 en Not specified 2025-01-18T08:29:51Z 2460693.8540625 Beta-blockers (especially propranolol) and the role of the sympathetic 0 [2,"smw-datavalue-wikipage-property-invalid-title","Has original text","nervous system\n\nRecenty the role of the sympathetic nervous system in cancer progression, and the\npotential role of beta-adrenergic antagonists (beta-blockers) have come into focus in\nsome corners of the cancer research community. Early studies linking stress to increased\nrates of cancer progression led to epidemiological studies showing lower rates of cancer in\nsubjects taking beta-blockers. Beta-blockers such as propranolol have more recently\nentered controlled clinical cancer trials.\n\nThe sympathetic nervous system is a division of the autonomic nervous system, most\noften associated with \u201cfight or flight\u201d responses. The sympathetic nervous system\ndepends upon catecholamines, mainly epinephrine (adrenaline) and norepinephrine\n(noradrenaline), which activate two classes of adrenergic receptors in target tissues\nthroughout the body: alpha and beta adrenergic receptors (which are further subdivided\ninto alpha-1, alpha-2, beta-1, beta-2 and beta-3 receptors).\n\nThe research and evidence concerning the link between the sympathetic nervous system\nand cancer progression has narrowed in more specifically on beta-adrenergic receptors\nand signaling. Animal studies in various cancer models demonstrated that stress\ncontributed to tumor progression, and these effects could be blocked with beta-blockers\n29\n\n(333). Investigated mechanisms are manifold, and include the following downstream\neffects of beta-adrenergic signaling: stimulation of pro-inflammatory cytokines such as\ninterleukin 6 and 8; increased recruitment of macrophages into tumors and increased\nmacrophage expression of genes such as TGFB, VEGF, IL6, MMP9, and PTGS2 (encoding\nthe COX-2 enzyme), which together promote angiogenesis, invasion, and\nimmunosuppression; inhibition of type 1 and 2 interferons, dampening down\ncell-mediated anti-cancer immunity, and decreased function of T-lymphocytes and\nnatural killer cells; activation of transcription factors that promote\nepithelial-mesenchymal transition, leading to tumor metastasis and invasion; and\nincreased production of pro-angiogenic growth factors and cytokines, such as IL-6 and\nVEGF. A 2015 review summarizes the current evidence for the sympathetic immune\nsystem\u2019s influence on cancer progression and the tumor microenvironment (334).\n\nClinical evidence supports the importance of beta blockers in cancer treatment. An\nepidemiological study in Taiwan (335) reported that the incidence of cancer was greatly\nreduced (30-50%) in subjects using propranolol for at least six months, including\nincidence of head and neck cancer and cancers of the esophagus, stomach, colon, and\nprostate. Incidence of brain cancer was too low in both the propranolol and\nno-propranolol groups to achieve a statistically significant reduction, although the risk of\nbrain cancer was also lower in the propranolol group. Confirming these findings is a\nrecent clinical study in the USA of ovarian cancer in which patients were divided into\nthose who used no beta blockers, those that used older non-specific beta blockers (such as\npropranolol), and those that used the newer selective beta blockers specific to beta-1\nadrenergic receptors. Ovarian cancer patients not using beta blockers had median\nsurvival of 42 months, those using the beta-1 selective agents had a median survival of 38\nmonths, and those using non-selective beta blockers (eg propranolol) had a superior\nmedian survival of 95 months (336).\n\nVicus Therapeutics, headquartered in Morristown New Jersey, is a company developing a\ncombination treatment they call VT-122, which consists of a \u201cchrono-modulated\u201d\nformulation of propranolol (a beta-blocker first approved by the FDA in 1967) and\netodolac (a non-steroidal anti-inflammatory first approved by the FDA in 1991). Both\ndrugs are off-patent and available as generics. Vicus has three clinical trials listed at\nclinicaltrials.gov: one, starting in 2007, tested VT-122 as a treatment for cachexia in\nnon-small cell lung cancer patients (NCT00527319); another, starting in 2010, is testing\nVT-122 in combination with sorafenib for hepatocellular carcinoma (NCT01265576); a\nthird, starting in 2013, is testing VT-122 for progressive prostate cancer (NCT01857817).\n\nNot listed on clinicaltrials.gov is a trial presented in abstract form for the 2015 ASCO\nmeeting, comparing low dose daily temozolomide (20 mg twice daily) with or without\nVT-122 for recurrent glioblastoma. 20 patients were assigned to low-dose temozolomide\nalone, and another 21 patients were assigned low-dose temozolomide plus VT-122.\nPatient characteristics are not given in the abstract apart from Karnofsky score, which\n30\n\nwas over 60 (median) in both groups. The most remarkable outcome was a median\noverall survival of 17.6 months in the low-dose TMZ + VT-122 group versus only 9.2\nmonths in the low-dose TMZ alone group. In the VT-122 group there were 5 complete\nresponses (24%) and 12 responses altogether (57%), compared to the corresponding\nfigures of 5% and 35% in the group receiving TMZ alone. One-year survival rate was 67%\nin the VT-122 group, and 30% with TMZ alone. Rates of thrombocytopenia, neutropenia,\nand anemia were higher in the VT-122 group. Statistical tests for significance were not\nreported in the abstract. Although this abstract leaves out vital information (enrollment\ncriteria, patient characteristics, progression-free survival data, statistical significance,\netc), a median survival of 17.6 months for recurrent glioblastoma is intriguing, while the\n9.2 months median survival in the low-dose TMZ alone group is closer to the average for\nrecurrent glioblastoma trials."] Beta-blockers (especially propranolol) and the role of the sympathetic# ERRa3f62c6665776505f0db7c26c19aebf1 Has treatment name 102 en Has treatment name