‘These inventions open up new possibilities for the development of a cure for cancer, including pancreatic cancer, which is extremely difficult to treat.’ A team of scientists from the Faculty of Biology at the University of Gdańsk, led by prof. Anna Herman-Antosiewicz, has been granted two patents for innovative inventions - two organic compounds, usnic acid derivatives, intended for use in the treatment of cancer.
The innovations were developed by a team led by prof. Anna Herman-Antosiewicz, including mgr Mariola Gimła, mgr Klaudia Żuczek, mgr Maciej Brodecki, dr Anna Pawlik and dr Tristan Reekie from the School of Science, University of New South Wales Canberra in Australia.
Usnic acid is a well-known biologically active compound isolated from lichens. It has a broad spectrum of activity, including antiviral, antifungal, antibacterial, immunomodulatory and anti-inflammatory effects. It is also known for its cytotoxic activity against cancer cells, but it must be used in high concentrations, which unfortunately are also toxic to normal cells. ‘New usnic acid derivatives have cytotoxic properties much stronger than usnic acid against tumour cells of the pancreas, cervix and breast, among others, and normal cells are less sensitive to them,’ says the creator, prof. Anna Herman-Antosiewicz. ‘Even relatively low concentrations of the derivatives inhibit the migration ability of cancer cells, cause characteristic changes in cancer cells resembling holes (so-called vacuolisation) and ultimately cause the death of these cells.’
The modifications made to the known structure of usnic acid have resulted in greater selectivity and cytotoxicity in the interaction with tumour cells. For this reason, the new compounds may be used as medicinal substances in cancer therapy. Since they induce a specific type of cancer cell death associated with their vacuolisation, they can also be used as inducers of this type of process in basic research. ‘These inventions open up new possibilities for the development of a cure for cancer, including pancreatic cancer, which is extremely difficult to treat due to the usually significant advancement of the disease at the time of diagnosis, as well as the characteristics of the tumours themselves, including the resistance of cancer cells to therapy and the limited penetration of drugs into tumour tissue. This important achievement emphasises the University of Gdańsk's commitment to research and development of future technologies,’ emphasises prof. A. Herman-Antosiewicz.
‘Usnic acid, a metabolite produced by lichens, has a number of interesting activities, including inhibiting the development of cancerous tumours. Unfortunately, it must be used in high concentrations, which are also toxic to healthy cells, especially liver cells. Our team's work aimed to modify the structure of this compound to obtain derivatives that are more selective and more toxic to cancer cells than to healthy cells,’ says prof. A. Herman-Antosiewicz. ‘We have obtained such derivatives that not only cause the death of pancreatic, cervical or breast cancer cells at a lower concentration than the starting compound but also inhibit their ability to move, which is a feature that enables cancer cells to metastasise. In addition, the death of cancer cells is accompanied by a specific type of stress (so-called endoplasmic reticulum stress) manifested by the appearance of large vacuoles in these cells that look like holes. It is also known that in cancer cells this stress is generally higher than in healthy cells, especially in pancreatic cells, so a slight increase in this stress caused by our derivatives has a fatal effect, but for cancer cells.’
The invention enables further research, including improving the way this drug is administered and identifying the characteristics of cancer cells that make them particularly sensitive to this drug, thus attempting to personalise its use.
‘Work on usnic acid derivatives with anti-cancer properties began in 2016 when a team of chemists from Australia sent a colleague studying lichens (dr Beata Guzow-Krzemińska) the first compounds to test their... antibacterial activity,’ says prof. A. Herman-Antosiewicz. ‘It turned out that as a result of the modification of the structure of usnic acid, it loses its antibacterial activity, but gains cytotoxic activity against cancer cells. Subsequently, more targeted changes and their biological effect were studied during the implementation of the Harmony grant from the National Science Centre in cooperation with a team of chemists from Australia. This resulted in several publications and patents, but above all knowledge about which elements of the usnic acid structure are important for the anti-tumour activity of its derivatives, how they can be improved, and what the mechanisms of their action are. What is more, two of the derivatives have been tested in vivo, on a mouse model with transplanted human breast or pancreatic cancer cells, and the results obtained are very promising.’
The invention has a very high potential for use in the treatment of tumours of various origins, especially pancreatic cancer, which has the lowest cure rate (5-year survival rate from diagnosis is around 9% of patients). This is because it is usually diagnosed at an advanced stage, the possibility of surgically removing the tumour is only possible for a small group of patients, and the tumours are highly resistant to chemotherapy.
The creator intends to continue research with the team to obtain formulations of usnic acid derivatives that will reach tumour tissue and target their action in cancer cells even more effectively (Opus project submitted to the NSC in cooperation with MUG and with the participation of specialists from the Faculty of Chemistry, UG and Australia).
The Intellectual Property Rights of the researchers' research results are coordinated and commercialised by the University of Gdańsk's Technology Transfer Office.
