Cancer patients rarely die from the primary tumor but rather from the metastases, even after successful tumor surgery. This is because cancer cells sometimes spread to other parts of body early in the disease, when the tumor is still very small and may not have even been discovered yet. To do this they must break away from the extracellular matrix and migrate into neighboring lymphatic vessels or blood vessels that transport them to new tissue, where they settle and proliferate.
Understanding the molecular mechanisms of metastasis is therefore a key piece of the puzzle in the fight against cancer.
More than ten years ago, Ulrike Stein at the Experimental and Clinical Research Center ( ECRC ) was able to discover an important driver of this process in human colorectal cancer: the metastasis-associated in colon cancer 1 ( MACC1 ) gene.
The ECRC is a joint institution of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association ( MDC ) and Charité – Universitätsmedizin Berlin.
When cancer cells express MACC1, their ability to proliferate, move around the body, and invade other tissues is enhanced.
Many types of cancers spread only in patients with high MACC1 expression.
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.
In the search for MACC1 inhibitors, it has been conducted drug screening with researchers at the European Molecular Biology Laboratory ( EMBL ) in Heidelberg, Germany.
They independently hit upon statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications.
This discovery was tested on various tumor cell lines, with favorable results: all seven drugs tested reduced MACC1 expression in the cells but to varying degrees.
Researchers have then administered the cholesterol inhibitors to genetically modified mice with increased MACC1 expression. This almost completely suppressed the formation of tumors and metastases in the animals. The benefits continued in the animals even after researchers reduced the dose relative to the amount that humans normally ingest.
Robert Preissner and researchers at the University of Virginia ( USA ) have 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.
The experimental studies and retrospective data analysis will now be followed up by a clinical trial. Only after that will it be possible to say with certainty whether statins actually prevent or reduce metastasis in patients with high MACC1 expression. ( Xagena )
Source: Clinical and Translational Medicine, 2022