Cholesterol-lowering drugs can also fight cancer, major new research finds
[Mar. 21, 2023: JJ Shavit, The Brighter Side of News]
Understanding the molecular mechanisms of metastasis is therefore a key piece of the puzzle in the fight against cancer. (CREDIT: Getty Images)
Statins, a class of drugs commonly used to lower cholesterol levels, may have an unexpected benefit in inhibiting the spread of cancer cells, according to a recent study by researchers from the Experimental and Clinical Research Center (ECRC) and Charité – Universitätsmedizin Berlin. Published in the journal Clinical and Translational Medicine, the study found that statins can inhibit the metastasis-associated in colon cancer 1 (MACC1) gene, which is responsible for promoting cancer cell metastasis.
Metastasis is the process by which cancer cells spread from the primary tumor to other parts of the body. According to the American Cancer Society, metastasis is the main reason why cancer is difficult to treat and why many cancer patients die. This is because metastasis often occurs early in the disease process, before the primary tumor has been detected or treated. The spread of cancer cells to other parts of the body can cause serious health problems, and it is often much more difficult to treat than the primary tumor.
The discovery of MACC1
The ECRC, which is a joint institution of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and Charité – Universitätsmedizin Berlin, has been studying the molecular mechanisms of metastasis for over ten years.
In 2009, Professor Ulrike Stein and her team at ECRC discovered the MACC1 gene, which is a key driver of metastasis in human colorectal cancer. MACC1 is also a biomarker of tumor growth and metastasis in more than 20 other solid tumors, including gastric, liver, and breast cancer.
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The role of statins
In their recent study, Stein and Dr. Robert Preißner of Charité found that statins can inhibit the expression of MACC1 in tumor cells. They conducted high-throughput drug screening with colleagues at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and found that statins were among the drugs that could inhibit MACC1 expression. They then tested the drugs on various tumor cell lines and found that all seven drugs reduced MACC1 expression in the cells to varying degrees.
The researchers then administered the drugs to genetically modified mice with increased MACC1 expression. They found that the drugs almost completely suppressed the formation of tumors and metastases in the animals. This effect continued even after the researchers reduced the dose to a human equivalent dose.
The benefits of statins
Statins have one big advantage over other drugs that might inhibit MACC1: they are already approved for use in humans to lower cholesterol levels. This means that they have already undergone rigorous testing for safety and efficacy, which could accelerate the process of obtaining approval for their use as a cancer treatment.
Statin treatment decreases tumour burden and metastasis formation in vivo. At day 24 of statin treatment, showed significantly weaker signals, indicating restricted metastasis formation in the liver. Bioluminescent signals from all ten animals over the time course of the experiment were quantified. (CREDIT: journal Clinical and Translational Medicine)
Preißner and scientists at the University of Virginia examined data from a total of 300,000 patients who had been prescribed statins and found that these patients had only half the incidence of cancer compared to the general population.
Stein advises against taking statins as a preventive measure without consulting a doctor and having their lipid levels checked, so as to ensure no serious side effects occur. She stresses that the experimental studies and retrospective data analysis will now be followed up by a clinical trial to determine whether statins can actually prevent or reduce metastasis in patients with high MACC1 expression.
Statin treatment decreases tumour burden and metastasis formation in vivo. At day 24 of statin treatment, showed significantly weaker signals, indicating restricted metastasis formation in the liver. Bioluminescent signals from all ten animals over the time course of the experiment were quantified. (CREDIT: journal Clinical and Translational Medicine)
The future of cancer treatment
The discovery that statins may be able to inhibit the expression of MACC1 in tumor cells is an important step forward in the fight against cancer. Metastasis is a major problem in the treatment of cancer, and if statins can reduce the risk of metastasis, it could lead to better outcomes for cancer patients.
Despite the potential benefits of using statins as a cancer treatment, there are also concerns about their potential side effects. Some common side effects of statins include muscle pain, liver damage, and an increased risk of developing type 2 diabetes. These side effects can be serious and may limit the use of statins in some patients.
Data pre-processing and cohort design. Patient records from databases at the Charité and UVA Health System were merged into a trans-Atlantic cohort. From the resulting 432 333 records, 31 010 were excluded (upper-right panel) due to incompleteness or contradictory information; this pre-processing yielded a final trans-Atlantic cohort of 277 980 patients. Of these, 53 113 were diagnosed with cancer, where ‘cancer’ is defined based on ICD10 codes in the range of ‘C00’ to ‘D48’ (excluding codes ‘D10’ to ‘D37’, which describe benign neoplasms). Co-medications prescribed along with statins (lower-left), as well as co-diagnoses with cancer and statin indications (lower-right), were included in the confounder analysis and calculated for both the full trans-Atlantic and 1:1 matched cohorts. (CREDIT: journal Clinical and Translational Medicine)
Furthermore, not all cancer patients may benefit from statin treatment. While the researchers found that statins could inhibit the MACC1 gene in tumor cells, not all tumors express this gene. Therefore, the efficacy of statins may be limited to certain types of cancer.
In conclusion, the research conducted by Ulrike Stein and Robert Preißner suggests that statins may have potential as a treatment for cancer. By inhibiting the MACC1 gene, which plays a key role in tumor growth and metastasis, statins could potentially prevent or reduce the spread of cancer cells.
However, further research is needed to determine the safety and efficacy of statins in cancer patients. Clinical trials will be necessary to determine whether statins can be repurposed as a cancer treatment and to identify which patients may benefit the most from this type of treatment.
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