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M2-PK Enzyme in Cancer Research
Category: Cancer Research | 29/04/2008 - 14:33:57
Cancer research is on the verge of an important change in direction. Two papers have just been published in 'Nature' which elucidate the influential role played by M2-PK in tumour metabolism.
M2-PK Enzyme - Cancer Research
Cancer cells can obtain their energy from the conversion of glucose to lactate, instead of breaking down sugar to CO2 and water. This confirms the 80 year old hypothesis of the German Noble prize-winner Otto Warburg, in which an altered energy production plays a decisive role in the development of cancer. The key enzyme 'M2-PK' plays a crucial role in this process, as reported in 'Nature', the world-renowned expert scientific publication, by scientists from the Harvard Medical School (13th March 2008).
Christofk, Cantley and other workers within their group present the results of their experiments in two papers* (abstracts available at http://www.nature.com/nature/journal/v452/n7184/abs/nature06667.html and http://www.nature.com/nature/journal/v452/n7184/abs/nature06734.html ). These findings represent a real change of direction in cancer research, whilst at the same time confirming the earlier findings of other scientists, such as Warburg, Eigenbrodt and Mazurek, who have shown that tumour cells express a characteristic isoform of the glycolytic key enzyme pyruvate kinase.
The principle of "aerobic glycolysis" as a survival strategy utilised by tumours was first described around 80 years ago by Otto Warburg. Eigenbrodt et al published results of research which established the importance of M2-PK in tumour metabolism from 1980 onwards and subsequently Mazurek and others have expanded our knowledge and understanding of the vital role played by M2-PK in tumour growth and metabolism (http://www.metabolic-database.com/html/m2-pk.html). M2-PK is the synonym for both the dimeric and tetrameric forms of the pyruvate kinase isoenzyme type M2 (also known as PKM2). It is the dimeric form of M2-PK which predominates in tumour cells, resulting in the accumulation of nucleic acids, phospholipids and amino acids necessary for tumour growth.
M2-PK Measurement and Screening
Commercial test kits already available for the measurement of M2-PK in blood and stool samples
M2-PK concentrations in faeces can be used for bowel cancer screening, and in EDTA-plasma for monitoring therapy response and disease progression in various cancers. Reliable test kits for the detection of this enzyme are already commercially available, developed and marketed by ScheBo Biotech AG from Giessen in Germany.
M2-PK screening for the early detection of bowel cancer and polyps
Clinical studies conducted in Germany, England and Ireland, which measured faecal M2-PK as a metabolic marker for the early detection of colorectal cancers, have shown that M2-PK has a sensitivity between 73% and 97%. This means that for every 100 people with a colorectal tumour, the various studies show that the Tumor M2-PK test will detect this in between 73 and 97 of them. For polyps bigger than 1cm, the sensitivity was 60%. The overall sensitivity for polyps of all sizes was 40%.
By measuring the enzyme M2-PK in faeces, bowel tumours and polyps can be detected with high sensitivity, without being dependent upon the presence of occult blood. Both bleeding and non-bleeding polyps or tumours can be detected. The result is not influenced by any specific foods, which means that no dietary restrictions are required before conducting the test. Haemorrhoids or other sources of blood in the stool do not lead to false positive results. These scientific findings represent a fundamental change of approach to the screening and early detection of bowel cancer and polyps.
Measurement of therapeutic response and monitoring in various cancers using M2-PK
Studies from international working groups have shown that M2-PK concentrations in EDTA-plasma samples from patients with gastrointestinal tumours (of the oesophagus, stomach, pancreas, colon or rectum), lung, breast, cervical or renal cell carcinomas, as well as melanoma, were significantly increased and correlated with tumour stage.
Therapy monitoring is an important field for the measurement of M2-PK in EDTA-plasma. This allows early recognition of the success or failure of a particular therapy and enables a prognosis to be reached on the chances of a "cure".
New active substances which target M2-PK successfully block tumour metabolism
ScheBo Biotech AG is not just a biotech company actively involved in the development of in-vitro diagnostics, but has also already developed very promising active substances which target M2-PK and other key enzymes, thereby blocking relevant steps in cancer metabolism. Pre-clinical studies with these innovative active substances have demonstrated major success in blocking cancer cells. The company is extremely confident that "through this new approach a fundamental breakthrough in new methods for cancer diagnosis and therapy will be achieved", according to board director Dr. René M. Kröger.
|Dr. René M. Kröger, |
Member of the Board of Directors,
ScheBo Biotech AG,
Tel: + 49 641 49960
Fax: + 49 641 499677
Dr Kroeger is a member of the Board of Directors of ScheBo Biotech AG, which has international headquarters in Giessen, Germany
Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC (2008). Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 452; 181 - 188.
Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC (2008). The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452; 230 - 234.