Breast cancer is today the most commonly diagnosed cancer in the world. The fight against it is still going on, and the most important weapon is to know the enemy thoroughly. However, in the face of many different types of breast cancer and a huge number of factors that may reduce the effectiveness of therapy, it is a challenge for medicine. It is not difficult to imagine a situation in which a patient goes to a doctor and undergoes treatment, but it does not give the expected results, despite the fact that it has been selected individually. For this reason, it is so important to understand the elements that affect the microenvironment of cancer – the network of cells and extracellular substances that surrounds it. It is these elements that can make the tumor resistant to any therapy. One of them is hypoxia, which has become the subject of research by Polish scientists from The Centre of Molecular and Macromolecular Studies of the Polish Academy of Sciences in Lodz: dr. hab. Markus Düchler, Łukasz Pęczek PhD, Karolina Żuk PhD and from the Department of Molecular Biology of Cancer, Medical University of Lodz: Izabela Zaleśna PhD, prof. dr hab. n. med. Arkadiusz Jeziorski and prof. dr hab. n. med. Małgorzata Czyż.
How do tumors disrupt the immune system?
The immune system recognizes and eliminates cancer cells, so for a tumor to thrive, it is necessary to disable the body’s immune mechanisms. Tumor cells secrete proteins for this purpose, which in turn results in the influx of suppressive cells, such as Tregs, into the tumor microenvironment. They are very effective in blocking the anticancer immune response, which allows the breast cancer to develop uncontrollably from now on.
Another challenge for the immune system is the wide variety of breast cancer microenvironment. Research by the aforementioned scientists from the Polish Academy of Sciences and the Medical University of Lodz on 33 patients with this type of cancer showed that all tumor samples showed extremely high heterogeneity. This means that in each patient, breast cancer – by modifying its microenvironment – increases its own complexity at the same time, making effective treatment difficult. This can be caused by many different factors, including hypoxia.
Effect of hypoxia on cancer cells
Hypoxia can be called a hallmark of cancer – it is found in cancer tissues in 90% of solid tumors. For many years, however, it was thought to be an accidental side effect of rapid tissue growth, neutral to the development of breast cancer itself. Subsequent studies, including the research of scientists from Lodz, lead to surprising conclusions. It turns out that tumor hypoxia is extremely beneficial for it because it increases resistance to radiotherapy and chemotherapy, changes the function of cancer cells, stimulating them to dedifferentiate, and promotes the formation of metastases. Oxygen, a life-giving gas for humans, present in the cancer microenvironment, becomes its enemy.
How can breast cancer cells adapt to hypoxic conditions? As explained by researchers, adaptation is associated with the activity of HIF factors that regulate the cellular response to low oxygen pressure. Excessive activity of this protein is observed in cancer, which in turn inhibits the production of immune cells in the patient’s body and enhances tumor growth. The researchers point out that targeting HIF proteins may therefore not only sensitize breast tumors to radiation and chemotherapy, but also interfere with the suppression of cancer’s immune system and therefore increase the effectiveness of the therapy.
How to use what we know?
We still don’t know enough about breast cancer. Research on its microenvironment, such as that conducted by Markus Düchler, Łukasz Pęczek, Karolina Żuk, Izabela Zaleśna, Arkadiusz Jeziorski and Małgorzata Czyż, are extremely important for this reason – they actually increase the chance of achieving the expected results of a given therapy. In addition, they are also an important means of developing the Polish market, giving Polish research centres the opportunity to establish strategic cooperation with foreign enterprises, whose common goal is to develop the most effective methods of treating patients with breast cancer. The potential of Polish companies that will use the results of this type of research projects can be appreciated around the world, and this will allow for the dynamic development of the Polish medical sector and national medical businesses.
The results themselves create space for completely new solutions in the field of breast cancer therapy. Hypoxia reduces the sensitivity of the tumor to treatment, while under hypoxic conditions, the further development of cancer depends to a large extent on HIF. Therefore, the use of oxygen delivery to the tumor microenvironment in therapy or conducting further research on the possibilities of inactivating HIF factors gives a chance to control this enemy, which is still dangerous for women around the world.
Breast cancer is the most frequently diagnosed cancer in the world, but not every diagnosed disease is cured. It turns out that the effectiveness of the therapy may be reduced by tumor hypoxia, which is the subject of research by scientists from the CBMiM PAN and the Medical University of Lodz. Their scientific development allows us to understand the relationship between hypoxia and the development of breast cancer and to create new solutions in the field of breast cancer treatment.
- Current and future burden of breast cancer: Global statistics for 2020 and 2040, Melina Arnold, Eileen Morgan, Harriet Rumgay, Allini Mafra, Deependra Singh, Mathieu Laversanne, Jerome Vignat, Julie R. Gralow, Fatima Cardoso, Sabine Siesling, Isabelle Soerjomataram, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465273/
- Rola komórek układu odpornościowego w mikrośrodowisku nowotworów – fragm., Joanna Kopeć-Szlęzak, https://www.czytelniamedyczna.pl/4241,rola-komorek-ukladu-odpornosciowego-w-mikrosrodowisku-nowotworow.html
- Limfocyty T regulatorowe i ich blokowanie w terapii przeciwnowotworowej, dr Agnieszka Góral, dr Angelika Muchowicz, prof. Jakub Golab, dr hab. Radosław Zagożdżon, dr Małgorzata Firczuk, http://www.stream.wum.edu.pl/pl/baza-wiedzy/195-limfocyty-t-regulatorowe-i-ich-blokowanie-w-terapii-przeciwnowotworowej
- The heterogeneous immune microenvironment in breast cancer is affected by hypoxia-related genes, Markus Düchler, Łukasz Pęczek, Karolina Żuk, Izabela Zaleśna, Arkadiusz Jeziorski, Małgorzata Czyż, https://www.sciencedirect.com/science/article/abs/pii/S0171298513001666?via%3Dihub
- Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat. Rev. Cancer 8, 180–192 (2008), Bristow, R. G. & Hill, R. P.