The evolutionary significance of TKTL1 suggests that there are many and diverse possibilities for applying our knowledge of this gene in new medical procedures – especially in the field of diagnosis and therapy of severe diseases.
Two Sides of the Same Coin
TKTL1 protects healthy cells, but also malignant cells. It ensures that the cells of our retina are not damaged by too many radicals, that sperm cells in the human testis are protected from DNA mutations, and that no errors occur during cell division. In all these cases, the protective mechanism is the switch from aerobic combustion metabolism in the mitochondria, during which free radicals are formed due to oxygen participation, to anaerobic fermentation metabolism without radical formation. Less energy can be obtained this way, but in certain situations this disadvantage is compensated by the fact that fermentation is much safer for the cells, especially at sensitive moments such as cell division.
However, cancer cells also take advantage of this mechanism. They use anaerobic fermentation metabolism to produce energy and thus also benefit from its additional effects:
- Rapid growth, since TKTL1-controlled fermentation metabolism provides sufficient building materials such as nucleotides.
- Protection from the immune system, since the lactic acid produced during fermentation metabolism acts as a barrier against immune cells.
- Possibility of spreading in the body (metastasis), since the lactic acid surrounding the tumor damages and destroys surrounding tissue, thus creating more space for the tumor.
- Ensuring the supply of the tumor tissue, by stabilizing the signal substance HIF-1α, which is formed in healthy cells when there is a lack of oxygen. Since this substance is stabilized by the presence of TKTL1 and is not degraded as intended, the new formation of blood vessels for the supply of the tumor tissue is ensured.
- Limitation of programmed cell death, since substances are formed by TKTL1 that reduce cytochrome c, which is important for apoptosis.
The evolutionary significance of TKTL1 suggests that there are many and diverse possibilities for applying our knowledge of this gene in new medical procedures – especially in the field of diagnosis and therapy of severe diseases.
Two Sides of the Same Coin
TKTL1 protects healthy cells, but also malignant cells. It ensures that the cells of our retina are not damaged by too many radicals, that sperm cells in the human testis are protected from DNA mutations, and that no errors occur during cell division. In all these cases, the protective mechanism is the switch from aerobic combustion metabolism in the mitochondria, during which free radicals are formed due to oxygen participation, to anaerobic fermentation metabolism without radical formation.
However, cancer cells also take advantage of this mechanism. They use anaerobic fermentation metabolism to produce energy and thus also benefit from its additional effects:
- Rapid growth, since TKTL1-controlled fermentation metabolism provides sufficient building materials such as nucleotides.
- Protection from the immune system, since the lactic acid produced during fermentation metabolism acts as a barrier against immune cells.
- Possibility of spreading in the body (metastasis), since the lactic acid surrounding the tumor damages and destroys surrounding tissue, thus creating more space for the tumor.
- Ensuring the supply of the tumor tissue, by stabilizing the signal substance HIF-1α, which is formed in healthy cells when there is a lack of oxygen. Since this substance is stabilized by the presence of TKTL1 and is not degraded as intended, the new formation of blood vessels for the supply of the tumor tissue is ensured.
- Limitation of programmed cell death, since substances are formed by TKTL1 that reduce cytochrome c, which is important for apoptosis.
TKTL1 as a Marker in Early Cancer Detection
It is not a big leap from the knowledge that TKTL1 promotes tumor growth to the question of whether this knowledge can be used for early detection, diagnosis or treatment of corresponding diseases.
A study at the University Medical Center Hamburg-Eppendorf tested 5,000 healthy volunteers with PanTum Detect® blood test, which detects the two enzymes TKTL1 and DNaseX (Apo10) in macrophages. If there was an abnormal test result, the suspicion was clarified in the subject by imaging.
The aim of the study was to determine whether PanTum Detect® blood test provided sufficient suspicion to justify the use of imaging. The study was able to confirm that it provided sufficient suspicion for follow-up examinations with imaging techniques such as MRI or PET/CT. It was thus able to identify those study participants for whom further examinations associated with radiation exposure and high costs are useful.
In addition to TKTL1, the researchers were interested in the biomarker Apo10. Apo10 detects an epitope of the endonuclease DNaseX, which plays an essential role in programmed cell death (apoptosis). In turn, a conspicuously high concentration of TKTL1 indicates that an increased cell division process of pathological cells is underway.
Since all types of cancer benefit from the above-mentioned factors, the detection of increased TKTL1 activity generally allows conclusions to be drawn about tumor activity (i.e. cancer or a precancerous condition). This is a real game changer, because existing screening tests and also novel blood tests for tumor markers are usually developed specifically for only one particular type of cancer.
TKTL1 as a Marker in Early Cancer Detection
It is not a big leap from the knowledge that TKTL1 promotes tumor growth to the question of whether this knowledge can be used for early detection, diagnosis or treatment of corresponding diseases.
A study at the University Medical Center Hamburg-Eppendorf tested 5,000 healthy volunteers with PanTum Detect® blood test, which detects the two enzymes TKTL1 and DNaseX (Apo10) in macrophages. If there was an abnormal test result, the suspicion was clarified in the subject by imaging.
The aim of the study was to determine whether PanTum Detect® blood test provided sufficient suspicion to justify the use of imaging. The study was able to confirm that it provided sufficient suspicion for follow-up examinations with imaging techniques such as MRI or PET/CT. It was thus able to identify those study participants for whom further examinations associated with radiation exposure and high costs are useful.
In addition to TKTL1, the researchers were interested in the biomarker Apo10. Apo10 detects an epitope of the endonuclease DNaseX, which plays an essential role in programmed cell death (apoptosis). In turn, a conspicuously high concentration of TKTL1 indicates that an increased cell division process of pathological cells is underway.
Since all types of cancer benefit from the above-mentioned factors, the detection of increased TKTL1 activity generally allows conclusions to be drawn about tumor activity (i.e. cancer or a precancerous condition). This is a real game changer, because existing screening tests and also novel blood tests for tumor markers are usually developed specifically for only one particular type of cancer.
