Polish scientists have developed and studied a chemical compound that shows strong activity against colon cancer cells while leaving healthy tissue largely unaffected, according to research conducted at several Polish institutions.
The compound, named DK-AT390HCl, was developed by researchers from the Cracow University of Technology, the University of Agriculture in Kraków, and the Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences.
“We already have more than a seed drug. This is an early version of a working therapeutic system,” said research team leader Damian Kułaga, PhD, from the Faculty of Chemical Engineering and Technology of the Cracow University of Technology, as quoted on the university’s website.
For several years, researchers at the Cracow University of Technology have been searching for chemical compounds with potential applications in the treatment of colorectal cancer (CRC) and triple-negative breast cancer (TNBC), the university said. As part of that work, more than 200 new molecules were designed and synthesised, with DK-AT390HCl ultimately selected for further study.
Initial tests showed no significant activity against triple-negative breast cancer cell lines. However, further biological studies conducted by Izabela Siemińska, PhD, a veterinarian at the Department of Infectious, Invasive Diseases and Public Health at the Faculty of Veterinary Medicine of the University of Agriculture in Kraków, demonstrated a different effect.
According to the university press release, the compound caused virtually no damage to healthy cells while having a very strong impact on colon cancer cells.
Kułaga said: “The therapies we know often cause serious side effects, affecting not only diseased but also healthy tissue. Some cancer cells are so ‘smart’ that they become resistant to a given drug, much like bacteria do to antibiotics.”
One of the mechanisms of action of DK-AT390HCl is its ability to inhibit autophagy in cancer cells. Autophagy is a natural cellular process in which cells recycle damaged proteins and organelles to obtain energy and materials for regeneration and growth. In cancer cells, particularly those with KRAS or BRAF mutations, autophagy can intensify under unfavourable conditions such as chemotherapy.
“We want to inhibit this process so that cancer cells have no way of defending themselves,” Kułaga said.
As part of the study, the scientists carried out a series of in vitro and in vivo assessments, including cytotoxicity testing, colony formation assays, tumour cell migration assays, determination of the maximum tolerated dose, evaluation of tumour mass reduction, and molecular testing of tumour tissue.
“The newly discovered compound selectively targets cancer cells without damaging healthy tissue. The results are therefore very promising for further colorectal cancer research,” said Siemińska, quoted on the university website. She added: “It is important to remember that the path from discovery to effective therapy for patients is long, often bumpy, and it requires many subsequent stages of research, including clinical trials.”
Colorectal cancer is among the most frequently diagnosed cancers worldwide and is the second leading cause of cancer-related deaths. Its rising incidence, including among people under the age of 50, has increased the urgency of developing more effective and safer therapies.
Other researchers involved in studying the biological efficacy of DK-AT390HCl included Laura Paradyak, PhD, Paweł Szczerbik, PhD, and Professor Zbigniew Arent from the University of Agriculture in Kraków.
The research team is planning further studies to address a key question: whether the compound, which has demonstrated anticancer effects in mice, will show similar activity in human tissues.
According to the university press release, the joint work of scientists from the Cracow University of Technology and the University of Agriculture in Kraków has resulted in four patents covering, among other aspects, the preliminary anticancer activity of DK-AT390HCl and its derivatives. One patent application, filed through the Patent Treaty Corporation, allows for protection outside Poland.
The university is considering selling the patent rights to the molecule to a Polish or foreign pharmaceutical company, with international patent protection in place. Kułaga said that “a partnership with a pharmaceutical company would expand the possibilities for flexible financing and conducting further research.”
The discoveries stem from two research projects: one funded under the 2022 Lider XII programme and another supported by the European Funds for Modern Economy programme through the Foundation for Polish Science.
Three centres participated in the Lider XII project. The Cracow University of Technology led the chemical research and compound synthesis, the Institute of Pharmacology of the Polish Academy of Sciences in Kraków carried out radioisotope studies, and the Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences in Wrocław conducted in vitro and in vivo biological testing of anticancer activity.
Additional contributors included researchers from the Cracow University of Technology and scientists from the Laboratory of Experimental Anticancer Therapy at the Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences.
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