Can statins really increase cancer survival?

Can statins really increase cancer survival?

Research on statins suggests lipophilic statins in particular may exert multiple anti-cancer benefits, including decreased tumour growth, angiogenesis, and metastasis. However, to date, much of the research supporting statins with cancer relies on in vitro cell studies or retrospective studies; and much of the criticism comes from epidemiology studies. We need some real, unbiased clinical trials.

Sugar feeds the primary cancer; fat spreads the cancer

In London, a group of oncologists at Care Oncology, have brought the issue of using off-label drugs to the cancer table. Their aim is to target glycolysis, glucose and cholesterol and impact the whole cancer process. This is exactly what CANCERactive has been telling people with cancer for nearly twenty years!

Cancer may use glucose to grow but it uses fat to spread.  Research shows that cancer burns sugar in the primary tumour but switches to burning fatty acids once it arrives in the adjacent lymph nodes. Furthermore, other research shows cancer cells 'load up' with lipids to begin their travels around the body and a third study shows that people with the highest levels of blood fats (cholesterol and triglycerides) develop more metastases and survive least. A number of cancers are worsened by high blood fat levels; and there is research with a number of cancers (for example, breast and lung cancer) where a low fat diet increases survival.

Go to: Saturated fat and cancer

Statins reduce serum cholesterol and there are a good number of studies showing that people with higher blood fat levels, especially saturated fat and LDL levels, develop more metastases and survive cancer least.  

Maybe cutting blood fats is enough to say that lipophilic statins will help increase survival. Any other benefits really have only been shown in the lab - the sort of studies oncologists diss for curcumin or berberine.. So here I have tried to focus on human research and meta-reviews.

Lipohilic vs Hydrophilic statins and cancer

Consistently throughout the research, the best results are obtained when using lipophilic statins (Atorvastatin, Lovastatin and Simvastatin, for example) rather than hydrophilic ones, as the former do not work only in the blood stream; they work in the tissues because they can cross membranes.

Statins may have several actions in cancer therapy

1. Cancer cell membranes require cholesterol for synthesis, and lowered cholesterol may reduce carcinogenesis and tumour progression.

2. Statins reduce prenylation (lipidation) - the attachment of hydrophobic molecules to proteins - and therefore signaling in tumour progression.

3. Statins reduce cytokines, and thus inflammation and metastasis (6).

Research on statins in the fight against cancer

While there is no doubt it is a crucial anti-cancer strategy to lower blood saturated fat levels, there is increasing research on the potential of statins - especially lipophilic statins - to increase survival. Young Wang Chae and his team produced a 2015 overview stating, "Statins have been investigated for a variety of cancers, early and late stage, and in combination with chemo and radiotherapy. So far promising results have been reported with statin use in pediatric brainstem tumours, early stage brest cancer, hepatocellular cancer (HCC), colorectal cancer, refractory or relapsed Multiple Myeloma, and refractory acute myeloid leukemia (AML)".

A number of cancers are reported on this website where people with the disease who consume a low fat diet survive longer.

Prostate cancer is well understood to be driven by higher blood fat levels - 

  1. In a 2019 study from Queen's University Belfast, while statins had no effect on reducing prostate cancer risk, the researchers found that cholesterol-lowering statins could reduce aggressive and fatal prostate cancer once a man had prostate cancer, by 24%. 
  2. In a 2020 prostate cancer study, this time from Sidney Kimmel Cancer Center in Philadelphia, 13,000 'high risk' men who had a Gleason score of over 8, were followed and those who took a statin along with metformin, had a median survival of 3.9 years, statins alone was 3.6 years, and metformin alone was 3.1 years, no higher than taking neither at 3.1 years.

  3. One study by Dr. Lauren Christine Harshman an assistant professor at both Dana-Faber and Harvard Medical School suggests that taking statins can slow down the rate of progression in prostate cancer where men are also taking hormone therapy (ADT). As we said above, prostate cancer progression is known to be linked to blood fat levels.

Colorectal cancer

  1. Patients where 40 mg Simvastatin was added to FOLFIRI showed longer survival times than previous studies.
  2. Patients with a KRAS mutation who added 80 mg of simvastatin to cetuximab and irinotecan exhibited longer survival times.
  3. A 2013 overview (Lockhead, Chan) stated that statins could modulate cancer cell growth, apoptosis and inflammation.
  4.  Statin use is linked with a lower risk of colorectal cancer.

Breast Cancer

  1. There is mixed research on statins with breast cancerOne Swedish study sought to clear this up and found that both pre-diagnostic statin use and post-diagnostic statin use was linked to lower levels of breast cancer-related death.
  2. A 2017 review suggested early stage breast cancer use of lipophilic statins was linked to a greater 5 year survival. In another study on 10-year survival, the use of lipophilic statins was linked to a 10% increased survival. No such benefits occurred with hydrophilic statins. This review did warn that long term usage might have a negative effect on risk and survival.

Ovarian cancer and endometrial cancer

  1. In a June 2020 study presented at the American Association for Cancer Research online conference, use of a statin was associated with a 40% lowered mortality in ovarian cancer. Where the statin was lipophilic, the figure rose to 43%. The biggest benefits came with patients who had High Grade Serous or Endometriod cancer.

Lung cancer

  1. A  2015 review concluded, in patients with lung cancer, there was evidence that people taking a statin, particularly simvastatin, had reduced mortality. This also seems to be true for those people taking the statin before diagnosis.
  2. In a March 2019 meta-analysis of observational studies on statins with 98,000 lung cancer patients, statins were believed to show significant survival benefits, especially when given after diagnosis. This was particularly significant with grade 4 stage 4 patients. 

Kidney cancer

      1. Early studies on statins with kidney cancer showed mixed results (possibly because of the type of statin used), so a 2017 meta-analysis set out to find the truth.  Across 12 studies and more than 18,000 patients, statins were noted to significantly improve the survival outcomes in kidney cancer.

Statins plus metformin

  1. There also seems to be more evidence for the simultaneous use of both metformin and a statin. One study showed that they synergistically inhibited endometrial cancer growth. Another showed that they reduced recurrence of prostate cancer in type-2 diabetes patients. The statin here was Simvastatin.

Laboratory studies

  1. Cholesterol is a major part of cell membrane structure and mevalonate produced in membrane synthesis is a precursor of dolichol which stimulates DNA synthesis and several cancer proteins. Mevalonate is also a precursor to GPP and FPP which regulate the ras and rho genes, which can cause cells to grow wildly. Ras and rho are involved in many cancers and statins like lovastatin and cerivastatin have been shown to block these genes (1)
  2. Statins also seem to increase apoptosis (cancer cell death) in cell lines from brain tumours, mesothelioma and cervical cancer.
  3. There is mixed research on angiogenesis. Some studies suggest statins reduce this; others suggest promotion of blood supplies in a review of statins and cancer in the Oncologist (2).

Statins and increased risk?

  1. There are strong arguments that statins can actually increase cancer risk due to modifying the immune response (3) and increasing the production of liver enzymes. And there is research showing an increased risk of cancer in the elderly when taking atorvastatin (4), and in people with a history of breast and prostate cancer (5).

Conclusions on statins for cancer patients

Some cancers - for example, Prostate and Lung cancer, are known to have strong links between blood fat and metastases. Others, e.g. Brain cancer are not.

It was really hard work to find anything that reseambled a real clinical trial on the Internet including using Care Oncology's references. Test tubes aren't believed on vitamin effects; should we believe them here, especially with an industry - the Statin makers - that will spin anything to make a drug look good. One large Observational study was much more 'for' statins than any other study I saw.

Having said all this, we at CANCERactive believe at its simplest level that fat spreads cancer and you must try to restrict that spread. This is why we are interested in statins, and lipophilic seem much better than hydrophilic.If your cancer is stage 3 or 4, what have you got to lose?

Cancer patients reading this might also look at the bioactive compound lycopene.  Lycopene from tomatoes is known to reduce prostate cancer risk, and aggressive and fatal prostate cancer too. This antioxidant also blocks glutamaminase - the enzyme that converts glutamine to glutamate (a fuel for cancer cells) - and attacks cancer stem cells, and 25 mg of lycopene beat statins in research.

Go to: Is Lycopene better than statins?

 

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References

  1. Soma MR, Corsini A, Paoletti R. Cholesterol and mevalonic acid modulation in cell metabolism and multiplication. Toxicol Lett 1992;64–65: Spec No1–15.
  2. http://theoncologist.alphamedpress.org/content/11/3/306.full#ref-48
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365486/
  4. Ann Intern Med. 2007 Jul 3;147(1):1-9.
  5. N Engl J Med. 2007 Oct 11;357(15):1477-86.
  6. Landskron G, De la Fuente M, Thuwajit P, et al. Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res. 2014;2014:1–19. 
2019 Research
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