Quantum leap in cancer early detection

Darmstadt, February 23rd 2024

It controls cell division and plays a crucial role in the development of the brain: TKTL1 has rightly been the focus of science and research for several years. It could also revolutionize the early detection and treatment of cancer. The discoverer of the gene, Dr. Johannes Coy, explains.

What distinguishes the Neanderthal brain from that of Homo sapiens? It couldn’t be size, so in 2022, research teams from the Max Planck Gesellschaft led by Wieland B. Huttner and the Nobel Prize winner for Medicine, Svante Pääbo, looked for other explanations. The result: during brain development, modern humans produce more nerve cells in the frontal lobe than their extinct relatives. The reason for this is a change in a single amino acid in the protein transketolase-like 1, or TKTL1 for short.

The formation of neurons in the fetal brain is considered an important factor for improved cognitive abilities during evolution. It may come as a surprise that TKTL1 plays a decisive role in this process: When Dr. Johannes Coy at the German Cancer Research Institute discovered the gene in the early 1990s, he postulated that the gene had a “special function in certain cells”. However, he was alone in this opinion at the time. “At the time, we were collaborating with the Sanger Center in the UK, and they said the gene was broken. I could forget about it,” explains the molecular biologist.

As a defective gene, it was ignored by researchers. But those days are now over: according to Coy, TKTL1 has gone “from being a defective gene to the most important gene in humans”. The enzyme not only plays a fundamental role in the development of the brain, but also in the entire cell process – from cell division to the repair of damaged cells.

Main factor in the formation of new cells

TKTL1 is the decisive factor in the formation of new cells, scientists summarized their findings in a study published in “Nature Communications” in 2019. The activation of TKTL1 boosts ribose production, which starts the cell cycle. “TKTL1 makes the decision and ensures that the building blocks are present,” says Coy, explaining the discovered push effect. In addition to ribose, the building blocks also include the molecule acetyl-CoA, as researchers at the University of Barcelona confirmed for the first time in 2016. According to Coy, it enables a cell to “100 percent convert” sugar into fat and thus efficiently convert it to build new cell components.

In general, the importance of TKTL1 can hardly be overestimated. People who lack the enzyme have a life expectancy of only 30 to 35 years. However, not only healthy cells benefit from TKTL1 metabolism. Unwanted cells, such as cells infected by viruses and cancer cells, are also beneficiaries of the TKTL1 metabolism. Coy therefore advocates the inclusion of TKTL1 “in the early detection and treatment of cancer”.

TKTL1 as a universal marker for tumor types

Due to its properties, TKTL1 is ideal for early cancer detection – as an early warning system for all tumor types and therefore as a universal marker. In early cancer detection, the earlier a tumor is detected, the more diverse the treatment options and the better the chances of recovery. Unfortunately, there are still no statutory screening measures in Germany for 55 percent of new cancer cases each year. The “PanTum Detect®” blood test from the Darmstadt-based biotechnology company Zyagnum AG, which Coy co-founded in 2007, could help close this screening gap.

Using the proprietary platform technology “EDIM®” (Epitope Detection in Monocytes), the stomach contents of macrophages, the scavenger cells of the immune system, are examined. These immune cells eliminate unwanted cells in the body. “Our immune system recognizes tumour cells and eats them up,” says Coy. The “PanTum Detect®” looks for increased concentrations of two markers in the macrophages – one of which is TKTL1 – which reflect processes that are present in all cells and therefore apply to all tumor types.

More targeted use of imaging

If the concentration of the first marker, the enzyme DNaseX (Apo10), is elevated, this is an indication that programmed cell death (apoptosis) has been disrupted. This is the case with cancer cells. Increased concentrations of DNaseX can be detected in all tumors – even benign ones. If a conspicuous amount of TKTL1 is found in the macrophages at the same time, it is clear that an increased division process of pathological cells is underway. Only TKTL1 creates the prerequisite for a benign tumor to turn into a malignant cancer, i.e. for cells to grow invasively.

If DNaseX (Apo10) and TKTL1 are elevated, the “PanTum Detect®” provides a conspicuous result, i.e. an indication of malignant cancer. “If you have the biomarkers, then you can use imaging in a more targeted way,” says Coy, explaining the great potential of TKTL1 and “PanTum Detect®” for early cancer detection. Various studies carried out at Tübingen University Hospital and elsewhere, both with supposedly healthy test subjects and with cancer patients, underline the performance of the blood test and markers: “PanTum Detect®” has a sensitivity of 95.2 percent (sick people are recognized as sick) and a specificity of 99.5 percent (healthy people are recognized as healthy).

“TKTL1 is a protective shield”

Coy also sees potential in cancer therapy: it is not surprising that chemotherapy and radiotherapy are not currently having the maximum success. “TKTL1 is responsible for the resistance of tumor cells,” explains the expert. Inhibiting the enzyme could therefore overcome resistance to standard therapies and make an existing therapy successful again. “TKTL1 is a protective shield,” the scientist explains the problem, “the protective mechanism is triggered and the chemotherapy fizzles out.” In order to effectively damage the tumor cell, the enzyme must be blocked. Benfo-oxythiamine (B-OT) can inhibit TKTL1 and thus the production of building blocks. This opens up new treatment options, as it makes chemotherapy and radiotherapy more effective. Resistance can thus be overcome.

Click here for the original link of the DUP magazine (only German version available).