Tracking down the molecular details of how stress accelerates tumor growth and progression is pointing to a potential new role for a class of drugs used to treat cardiovascular disease and related conditions.
Years of research by Anil Sood, M.D., professor in Gynecologic Medical Oncology and Cancer Biology, show that stress hormones fuel progression of ovarian and other cancers, and that beta-blockers 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, targeting 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 activation helps ovarian cancer progress and spread, so these drugs might have a new role for cancer.”
Sood’s findings include:
- When mice with ovarian cancer are stressed, their tumors grow and spread more quickly, but the effect can be blocked by the beta-blocker propranolol.
- Chronic stress triggers a chain of molecular events that protects breakaway ovarian cancer cells from automatic destruction. Heightened levels of the fight-or-flight hormones epinephrine and norepinephrine permit malignant cells to safely leave the primary tumor — a necessary step in cancer metastasis and progression — and avoid a cell-death mechanism called anoikis.
- When norepinephrine hits its target — the beta-adrenergic (ADRB) receptor — on tumor cells, it activates Src, a master regulator of cancer cell survival proteins, through another protein called PKA. Stress-activated Src is like a dam opening, only the flood is a chain reaction inside cells that promotes cell survival, mobility, invasion of neighboring tissue and creation of new blood vessels to supply
Beta-blockers plug the ADRB receptor, blocking activation by norepinephrine and other hormones. Norepinephrine is the most abundant stress hormone found in ovaries.
Sood and colleagues analyzed data on outcomes of cancer patients treated with beta-blocker drugs from the Food and Drug Administration Adverse Event Reporting System. They found that mortality in patients treated with a beta-blocker fell by an average of 17% across all major cancer types, with a nearly 15% decrease in mortality among patients with ovarian and cervical cancers.
Sood continues to study biological mechanisms that may be affected by stress with the aim of identifying cancer patients who are most likely to benefit from beta-blockers and other stress interventions.