Cancer is a major global health challenge, with millions of people diagnosed with the disease every year. Despite significant advancements in cancer treatment, the disease remains a leading cause of death worldwide. One promising approach to cancer treatment is the use of targeted therapies that specifically target cancer cells while leaving healthy cells untouched. Recently, researchers have been exploring the use of drug targeting techniques to attack cancer cells that are under stress.
This approach involves identifying specific biological pathways that cancer cells use to adapt and survive when they are under stress and developing drugs that target those pathways. In a recent clinical trial, a team of researchers tested a drug that targets stressed cancer cells in patients with solid tumors. The results of the trial were promising, with the drug demonstrating efficacy in reducing tumor growth and improving overall survival rates. This exciting development could pave the way for the development of new therapies that could improve the lives of millions of people with cancer.
According to a study published by Oncogene and as reported by Technology Networks, the Norwegian University of Science and Technology (NTNU) and APIM Therapeutics, an NTNU spin-off, have developed a cancer drug called ATX-101. After 18 years of research and over €20 million spent, the medicine has been tested on 20 terminally ill cancer patients who had exhausted all available treatments.
The medicine has shown promising results, and the cancer stopped growing in 70% of the patients who received the medication. Twelve continued the medication and were stable for 18 weeks, while one woman took the medication for 17 months and was stable for over two years. These results were published in a recognized cancer research journal.
The testing took place in Australia, where there are clinics that specialize in testing new medicines. The primary aim of the testing was not to check whether the medicine worked but rather to determine whether it was toxic to humans. The medicine was previously shown to both keep cancer at bay and defeat it in laboratory and animal experiments. The research was led by Professor Marit Otterlei, who is a professor of molecular medicine at NTNU.
Cancer is a result of damage to the cell’s DNA/genetic material, causing the cells to divide uncontrollably. Eventually, damaged cells accumulate and form a cancerous tumor. “Cancer cells are more stressed than other cells. However, they don’t die but continue to grow even when they are damaged. Conventional cancer treatment with chemotherapy puts more stress on the cancer cells so that the cells eventually do die. Chemotherapy affects all cells, including the normal ones, such as in the hair follicles, and thus affects the whole body with many side effects like hair loss,” says Otterlei.
The new cancer medicine that Otterlei has developed, ATX-101, only works on stressed cancer cells and leaves the other healthy cells in the body alone. One of the differences with this medicine is that cancer patients avoid losing their hair. “ATX-101 can be used as the only treatment. It can stabilize the cancer, as shown in the recently published studies, but the medicine can also help chemotherapy work even better so that you don’t have to have so much of it,” says Otterlei.
Simply put, the new cancer drug destroys cancer cells’ ability to handle stress so that they die or stop growing. In slightly more complicated terms, the new cancer drug is a peptide that contains a special binding sequence, APIM, which is found in many different proteins that bind to a coordinator molecule called PCNA. More than 500 proteins can potentially bind to this coordinator molecule.
“Half of the proteins contain the binding sequences that we discovered and yielded the name APIM for the sequence. We found that the APIM sequence is used to bind to PCNA mainly during stress, and it’s important for regulating stress in the cell. By blocking these bonds, the stress regulation will be destroyed,” says Otterlei.
The path from the biological discovery in the lab to applying this knowledge to treat people has taken 18 years. The first obstacle was to create a medicine that worked in the same way as biological discovery. Otterlei and the team were able to create the medicine after many years of repeated trial and error, which then enabled them to obtain a patent.
All the basic research is being carried out at NTNU, but since a university cannot be a commercial actor and produce medicine, Otterlei had to find a company. The team also worked to understand how the coordinator molecule PCNA regulated different stress functions. Otterlei and her colleagues at NTNU published an article that showed that PCNA has a newly discovered role as a regulator of the metabolism in our cells.
