Scientists describe new mechanisms controlling cancer cell division

Current treatment options for advanced cutaneous melanomas are limited. Drugs that inhibit the division of tumour cells by interfering with their signalling pathways work quickly, but only in the short term. Over time, the cells develop resistance to them and the tumour returns. This is why melanoma is one of the most aggressive cancer diagnoses, with around 2,500 people a year in the Czech Republic, increasingly including younger people. Scientists at Masaryk University Faculty of Medicine have discovered new fundamental mechanisms controlling the division of cancer cells, which may become a target for further drug development, not only in the field of skin cancer.

The study, published in the Proceedings of the National Academy of Sciences, one of the most cited scientific journals, focuses on the eIF4F protein complex, which plays a key role in regulating the ERK signaling path, a process that controls the growth and proliferation of cancer cells. "Previous research has shown that eIF4F is involved in melanoma cell resistance to treatment, but it was not entirely clear what the mechanism behind this was. Our study shows that the activity of the ERK path, is closely linked to the activity of eIF4F," says Mgr. Stjepan Uldrijan, CSc. from the Department of Biology at Masaryk University Faculty of Medicine, whose research group is also part of the National Cancer Research Institute.

While it was previously thought that the more active the ERK signalling path is, the more cancer cells divide, new research suggests that too much ERK path activity is detrimental to cancer cells, which then stop growing and die as a result. Research by the Brno scientists has shown that the function of the eIF4F protein complex is essential for dampening excessive ERK path activity in melanoma cells and that without its proper function, control of the activity of this signaling path is severely impaired. "If we could develop a drug that targets eIF4F directly, we could disrupt the regulatory mechanisms of cancer cells and prevent them from dividing further," Uldrijan summarises the main contribution and suggests another potential direction for research.

Although the research at this stage covers "only" basic cancer cell biology, it was until now uncharted, and one that other research teams or the pharmaceutical industry can rely on - it may also significantly facilitate the identification of compounds that could act on the eIF4F protein complex. "There are teams around the world looking for eIF4F inhibitors. We are also trying to do this ourselves, and we have already identified some new molecules that could be potential drug candidates," reveals Uldrijan.

The discovery of the importance of eIF4F could open up possibilities not only in the treatment of most patients with cutaneous melanoma. The findings of Uldrijan's team so far suggest that the mechanism described also applies to other types of tumours. "Exactly which ones, we want to look into in the future. In any case, it is not only us who have the door for further research opened," he concludes.