At a recent meeting of the American Society of Gynecologic Oncology in Los Angeles, CA., Anil Sood, MD, and colleagues from the MD Anderson Cancer Center in Houston, reported that patients with advanced ovarian cancer had significantly better survival if they took beta blockers.
In the past few years, more than a dozen studies have suggested that beta blockers hold substantial potential for therapeutical interventions in cancer.
Another recent study also indicates that a combination of beta-adrenergic antagonist and cyclooxygenase-2 inhibitor improves survival rates in murine models of postoperative metastasis. All these studies are based on the concept that catecholamines (CAs) through stimulation of beta-adrenoreceptors (ADRs) are involved in tumor development and/or tumor-related immunosuppression.
Catecholamines, the end products of the sympathetic nervous system, are major components of the autonomic nervous system and the peripheral stress system. It appears that CAs are able to affect tumor cells directly – through effects on tumor growth, angiogenesis, and migration or invasion, or alternatively, they may affect tumor growth, indirectly – through effects on the immune system (for example, through a multi-level immunosuppression).
The studies mentioned above indicate that the beta-ADRs antagonists, also known as beta blockers might exert beneficial effects by ‘blocking’ beta-ADR-mediated signaling pathways involved in these processes.
Interestingly, and along these lines, new research indicates that high tumor norepinephrine (noradrenaline) levels correlate with the tumor grade and stage, and that low social support and depression are associated with elevated intratumoral CAs in ovarian cancer patients (Lutgendorf SK et al., Brain Behav Immun, 2009, 2011). Also, CAs increase the expression of the potent pro-angiogenic cytokine interleukin 6 in ovarian carcinoma cells (Nilsson MB et al., J Biol Chem, 2007). Moreover, human ovarian cancer cells exposed to CAs exhibit lower levels of anoikis, the process by which cells enter apoptosis (Sood AK et al., J Clin Invest, 2010).
In the American Society of Gynecologic Oncology meeting’s report by Anil Sood et al., the multicenter retrospective study identified patients with stage III or IV ovarian cancer and compared records of patients who had been treated or not with beta blockers.
The analysis involved 1,425 patients, including 269 patients whose records documented the use of beta blockers. Of note, the survival difference more than doubled in the subgroup of patients treated with nonselective beta blockers.
This report supports and adds additional insights into the potential and novel therapeutic applications of beta blockers in cancer, and may suggest that further studies are warranted. More information for this study is available on medpagetoday.com.
