In a first-of-its-kind study, researchers at MD Anderson have demonstrated a benefit in overall survival among epithelial ovarian cancer (EOC) patients receiving generic heart medications known as beta-blockers.
Survival was shown to be greatest among those prescribed first-generation nonselective beta-blockers. According to investigators, the drugs block the effects of stress pathways involved in tumor growth and spread. With further research, they may also prove beneficial in conjunction with other treatment regimens and across other cancer types.
This study builds on a large body of research by principal investigator Anil Sood, M.D., professor of Gynecologic Medical Oncology and Cancer Biology at MD Anderson. It shows that stress hormones fuel progression of ovarian and other cancers, and beta-blockers — among the most proven drugs in cardiovascular medicine — might be a new way to stifle that effect.
“Beta-blockers treat a variety of conditions, such as heart disease, high-blood pressure, glaucoma and migraines. They target a receptor protein in heart muscle that causes the heart to beat harder and faster when activated by stress hormones,” Sood says. “Our research has shown that the same stress mechanisms impact ovarian cancer progression, so these drugs could play a new role in cancer treatment.”
Published in the journal CANCER, the findings are the result of a multi-institutional retrospective analysis of the medical records of 1,425 women with ovarian cancer treated
between 2000 and 2010.
Researchers compared overall survival among patients with documented beta-blocker use during chemo and those without.
Among the 269 patients who received beta-blockers, 193 (71.7%) received SBBs and the remaining patients received NSBBs. The research team found:
For patients receiving any beta-blocker, the median overall survival was 47.8 months versus 42 months for nonusers.
Median overall survival based on betablocker receptor selectivity was 94.9 months for those receiving NSBBs versus 38 months for those receiving SBBs.
Even among patients with hypertension, a longer median overall survival was observed among users of NSBBs compared with nonusers (90 months versus 38.2 months).
According to Sood, the usefulness of beta-blockers was unclear until now. “The ability to show improved survival using nonselective agents, which inhibit a specific stress pathway, is the culmination of years of research into ovarian cancer biology and pathogenesis.”
Although further study is needed, Sood says these results highlight the importance of the beta-2 adrenergic receptor, a signaling pathway important to ovarian carcinogenesis and targeted by nonselective beta antagonists (NSBBs) versus the beta-1 adrenergic receptor pathway targeted by selective agents (SBBs).
Sood talked to Cancer Frontline about the new findings, how they relate to his earlier research and what this new discovery means for patients.
Your earlier research has shown that stress hormones fuel progression of ovarian and other cancers, and beta-blockers might be a way to slow or stop that. How does this study build on that research?
In the present study, we examined whether the type of beta-blocker matters with regard to clinical outcomes. Consistent with the previous research from our group and others, broad (nonselective beta antagonists) beta-blockers were associated with better clinical outcomes.
How does stress affect tumor growth?
Chronic stress and related hormones — the so-called fight-or-flight hormones — can stimulate tumor growth via beta adrenergic receptors, which are key to ovarian carcinogenesis and targeted by NSBBs.
What would you tell ovarian cancer patients who ask about taking beta-blockers? Is it too soon to recommend ovarian cancer patients take beta blockers?
It’s too soon to prescribe beta-blockers for routine use, but feasibility studies are ongoing.
What other cancer types could this potentially benefit?
Other cancers that express beta-adrenergic receptors could also be relevant here. Those include colon, breast and other cancers.
Where does your research go from here?
Clinically, we’re carrying out prospective feasibility studies at present. Following these studies, we would like to conduct others to understand the effects of these drugs on specific biomarkers before starting larger-scale studies. Preclinically, there’s still a lot to understand. For example, we’re looking at the role of nerves that deliver the stress hormones to the tumor. We want to determine what role the nervous system plays in the spread of cancer.