Many people have to take statins to lower their cholesterol levels. But statins may be able to do even more: Researchers led by Ulrike Stein of the Experimental and Clinical Research Center (ECRC) and Robert Preißner of the Charité report in "Clinical and Translational Medicine" that these drugs inhibit the expression of a gene: MACC1 that promotes cancer cell metastasis. Since 2018, the SPARK-BIH program has supported Ulrike Stein's long-standing work to characterize MACC1 as a key factor and biomarker for tumor growth and metastasis and to identify inhibitors of this gene.
Understanding the molecular mechanisms of metastasis is a key piece of the puzzle in the fight against cancer. More than ten years ago, Professor Ulrike Stein and her lab at the ECRC were able to discover an important driver of this process in human colorectal cancer: the metastasis-associated in colon cancer 1 (MACC1) gene.
“Many types of cancers spread only in patients with high MACC1 expression levels,” Stein explains. MACC1’s role as a key factor and biomarker of tumor growth and metastasis – not only in colorectal cancer, but in more than 20 solid tumors such as gastric, liver and breast cancer – has since been studied by many other researchers worldwide and confirmed in more than 300 publications. Now together with Dr. Robert Preißner of Charité, Stein has discovered what could disrupt metastatic progression in such cases: Statins, which are prescribed as cholesterol-lowering drugs, inhibit MACC1 expression in tumor cells. The scientists are presenting their findings in the journal Clinical and Translational Medicine.
In their search for MACC1 inhibitors, the researchers conducted high-throughput drug screenings with colleagues at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. They independently identified upon statins. The scientists then administered the cholesterol inhibitors to genetically modified mice with increased MACC1 expression. This almost completely suppressed the formation of tumors and metastases in these animals. “What is particularly remarkable is that the benefits continued in the animals even after we reduced the animal dose to a human equivalent dose,” Stein says.
Statins have one big advantage: they are already approved
Robert Preißner and scientists at the University of Virginia also examined data from a total of 300,000 patients who had been prescribed statins. This analysis found a correlation: “Patients taking statins had only half the incidence of cancer compared to the general population,” Preißner explains.
Stein strongly advises against taking statins as a preventive measure without consulting a doctor and having lipid levels checked, so as to ensure no serious side effects occur.
“We are still at the very beginning,” the scientist stresses. “Cell lines and mice are not human beings, so we cannot directly transfer the results.” The experimental studies and retrospective data analysis will now be followed up by a clinical trial, she says. Only after that will it be possible to say with certainty whether statins actually prevent or reduce metastasis in patients with high MACC1 expression.
Bjoern-O Gohlke et al (2022): Real-world Evidence for Preventive Effects of Statins on Cancer Incidence: A Trans-Atlantic Analysis, in: Clinical and Translational Medicine, DOI: https://doi.org/10.1002/ctm2.726