Early cancer screening is an important tool. Those who are insured are entitled to the benefits of these provisions – but too few use them. Colonoscopy, which is carried out as a statutory provision procedure from the age of 55 on and may be repeated after ten years, is only used by around 20 per cent of German citizens who are entitled to it. If it were possible to do colorectal cancer screening via a blood test, the participation rate would probably look different. Science fiction? True. However after their recent discoveries scientists at the Charité and the Max Planck Institute for Molecular Genetics in Berlin have this possibility in mind.
Molecular markers for colorectal cancer discovered
“How was it possible, using mouse models for colon cancer, for a preserved pattern involving around 13,000 identify epigenetic changes to be identified, in which cancer cells differ from healthy cells? The alterations have already been observed in very young mice in which the APC gene, a tumor suppressor, is defective”, says Dr. Markus Morkel, leader of the study. This means that these mutations brought about the epigenetic changes. These alterations do not necessarily have a functional role in the progression of cancer, but the researchers found that a large proportion of these changes are also shown to be present in human colon cancer tissue. These patterns consequently appear to be highly conserved during evolution, which is something important for a marker.
Recognition before the cancer develops?
Armed with this set of markers for cancer cells, the scientists under Dr. Morkel proceed in their search for clues in the blood. Since tumour cells not only divide uncontrollably but also go into uncontrolled apoptosis, there is quite a lot of free tumour DNA in the blood. Therefore epigenetic alterations in the form of attached methyl groups can also be found there. As the next step on the path to a simpler test option, what now needs to be proven is whether DNA and epigenetic changes are detectable in the blood of cancer patients.
Then the scientists will test whether positive detection capability can be gradually shifted to an ever earlier point in time. Since epigenetic changes with cancer are already triggered by a causal mutation in the APC gene, a gene of the Wnt/ Beta-catenin signal transduction pathway, the alteration would therefore need to be detected at an early stage at which the pre-cancerous tissue could still simply be removed from the intestine – making it an important prerequisite for very useful screening work.
Epigenetics and cancer – a promising combination
Epigenetic patterns are being researched with other cancers as well. In gastric cancer, patterns in tumours and cell lines can be found which allow differentiation of aggressive from less aggressive variants. In addition, scientists are trying to use epigenetic processes in anti-cancer therapies. In breast, liver and kidney cancer an enzyme from the histone deacetyltransferase group, HDAC11, undergoes the epigenetic changes. In healthy tissue however, the enzyme seems to play no important role. Therefore, researchers at the German Cancer Research Center in Heidelberg hope that by using the targeted suppression of HDAC11 cancer cells can be switched off selectively, something which has in cell culture experiments already worked.
Whether it be methods for early diagnosis of cancer, or for therapy – there seems to exist great potential in epigenetics. We can look forward to seeing what trends will emerge in the coming years.