Beta-blockers could provide extra years for cancer patients

Beta-blockers could provide extra years for cancer patients

Research studies on the non-specific beta-blocker Propranolol show it reduces stress hormone-induced cancer progression and provides significant increases in survival times for patients with breast, prostate, lung, colorectal, ovarian and many other cancers.

What are beta-blockers?

Beta-blockers are cheap, well known drugs prescribed for hypertension (high blood pressure), migraines, glaucoma and for arrhythmia (irregular heart beat).

How do beta-blockers work?

Beta-blockers are also called beta-adrenergic blocking agents and work by blocking receptors for the stress hormones adrenaline (epinephrine) and noradrenaline (nor-epinephrine), and thus calming the heart beat and reducing blood pressure.

There are receptors in other tissues and beta-blocker drugs fall into three categories, specific for the heart, and ‘non-specific’ for other organs and tissues. It is the non-specific beta-blockers that have most effect with cancer.

Beta 1 receptors are found in the heart and kidneys.

Beta 2 receptors are found in the lungs, liver, uterus, skeletal muscle, smooth muscle and gastrointestinal tract.

Beta 3 receptors are found in fat cells.

N.B. Beta-blockers are not without their side-effects and you should consult with your doctor before taking them.

Why might Beta-blockers be important in cancer?

Chris Woollams, former Oxford University Biochemist writes, “It’s not cancer that kills you, it’s metastasis (cancer spread). And that’s the goal for many researchers – stopping metastases. Stress is a big biochemical factor in promoting and driving metastasis.

For example, 2019 research from the University of Basel (1) has shown that an increase in  stress hormones in breast cancer causes an increase in glucocorticoid receptors in distant organs in the body, and that both are linked to higher levels of metastasis. Worse, the distant receptors can even modify the cancer, making the new tumours less receptive to the drugs.

UCLA have a Stress Management Laboratory specialising in cancer and they have proven that people who actively manage their stress – and stress hormone levels – survive longer. They have been using natural ways to do this – recommendations include counselling, a colourful Mediterranean Diet, taking fish oils, exercise and especially yoga, and meditation. This is because certain anti-inflammatory foods along with the production of endorphins and opioids can neutralise the effects of stress hormones. 

We also know that the Ayurvedic herb Ashwagandha (2) is an adaptogen and can neutralise stress hormones. Beta-blockers can also stop or greatly reduce the effects of stress hormones in cancer.

So, is there actually research on Beta-blockers increasing cancer survival? 

Breast Cancer and beta-blockers

The above study was not the first with breast cancer. In 2012, researchers from Vanderbilt Center for Bone Biology showed in mice(3) that stress hormones had the ability to make bones more receptive to cancer. Dr. Florent Elefteriou demonstrated that stress hormones provoke a typical ‘fight or flight’ activation of the sympathetic nervous system and that this primed the bones. Stress hormones are proven to remodel the bone structure anyway, and this same mechanism creates a more favourable environment for the cancer to attack. Currently drugs such as Denosumab attempt to strengthen bones against attack.

Evidence from the Vanderbilt cancer clinic supported this. People whose cancer and/or treatment had made them stressed or depressed had shorter survival times. Since both stress and depression activate the sympathetic nervous system, Elefteriou’s team injected mice with fluorescent breast cancer cells, then used a drug that mimics sympathetic system stress activation. Sure enough, the cancer cells moved towards the bones as soon as stress hormones were heightened; a molecule dubbed RANKL known to break down bones was more prevalent in the bones, and more lesions were found.

The researchers then went on to show that a beta-blocker called Propranolol could block this effect.

In a 2017 study on stress-induced metastatic breast cancer progression to the lungs (4) the researchers suggested both Propranolol and Salbutamol would be effective at limiting this effect.

Ovarian Cancer and beta-blockers

In a retrospective study(5), researchers from MD Anderson showed that women with ovarian cancer who were taking beta-blockers during their chemotherapy, lived on average more than four years longer than those who were not. The type of beta-blocker was however important. Those who took cardiovascular beta-blockers (Beta1), showed a modest gain in survival from 40 to 42 months on average. However, this who took a non-selective beta-blocker (Beta2 and Beta3), the median overall survival climbed from 38 months to 95 months.

An overview(6) on the work of Professor Anil Sood with gynaecological cancers it concludes that stress hormones actually prevent ovarian cancer cells from breakdown and destruction. Noradrenaline actually prevents cancer cells from death, whilst stimulating metastasis, the formation of new blood supplies and mobility and invasion of tissues. Stress actually promotes cancer cells to leave the primary tumour, and Sood has shown that stress can promote Vascular Endothelial Growth Factor (VEGF) while Beta-blockers can stop this.

Sood also argues that more general Beta 2 and Beta 3 blockers offered better outcomes than specific Beta 1 blockers and that this fact was causing confusion in research results. In mice where tumours grew and spread more quickly under the effects of stress hormones, the effect can be blocked by the non-specific Propranolol.

Lung cancer and beta blockers

In another retrospective MD Anderson study, this time of 722 patients having radiotherapy with non-small cell lung cancer, both less metastases and an increase in survival times were noted(7). 

Colorectal cancer and beta-blockers

It may be that simply taking beta-blockers on diagnosis is not beneficial, and that their benefits are more linked to events (such as having chemo or radiotherapy), or to stage.

In a study (8) with CRC, no benefit was found for patients who were taking beta-blockers from the outset, but those who were stage IV and took non-specific beta blockers had an increase in survival times from 20 months to 37 months.

There are several studies that show stress and cigarette smoking stimulate growth in CRC, but as long ago as 2001, Massur et al showed beta-blockers could limit tumour progression(9). They confirmed the non-specific beta-blocker Propranolol was effective but not the Beta1 agent atenolol.

Improving cancer survival with beta-blockers - summary

Certainly the type of beta-blocker seems crucial and the non-specific (i.e. not for specific cardiovascular/blodd pressure issues) beta-blocker Propranolol seems the drug of choice for most cancers.

In a general review(10) of beta-blockers showing effect by cancer type, Propranolol is referenced as offering reduction of tumour progression and increases in survival times for multiple cancers such as breast cancer, ovarian cancer, lung cancer, pancreatic cancer, melanoma, prostate cancer, stomach cancer, leukaemia, angiosarcoma and nasopharynx cancer.

If you have cancer, the science is there and growing and this has to be information worth considering for your Complementary and Integrative anti-cancer programme.

Go to: Repurposing old drugs to fight cancer

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Ref: 

  1. https://www.canceractive.com/article/stress-hormones%20linked%20to%20breast%20cancer%20spread
  2. https://www.canceractive.com/article/ashwagandha-reduces-cortisol-and-chronic-inflammation-in-the-body
  3. http://news.vumc.org/2012/07/18/stress-breast-cancer-metastasis/
  4. https://www.ncbi.nlm.nih.gov/pubmed/28359245
  5. https://onlinelibrary.wiley.com/doi/10.1002/cncr.29392
  6. https://www.mdanderson.org/publications/conquest/betting-on-beta-blockers.h34-1589046.html
  7. https://www.ncbi.nlm.nih.gov/pubmed/23300016
  8. https://onlinelibrary.wiley.com/action/doSearch?AllField=lung+cancer%2C+beta+blockers&SeriesKey=10970142
  9. https://link.springer.com/article/10.1007/s00432-014-1658-7
  10. https://www.sciencedirect.com/science/article/pii/S1044579X13000850#bib0040

 

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