Scientists Propose a New Way to Combat Metastases

Localized tumours are considered relatively harmless – they are easily treatable and often do not recur. However, most cancerous formations tend to metastasize, meaning they have the ability to spread throughout the body via the bloodstream or lymphatic system. By forming secondary foci in the bones, lungs, liver, brain, and other organs, they become life-threatening. This is why researchers studying cancer are actively seeking ways not only to effectively stop tumour growth but also to block their metastasis.

A new weapon against metastases will soon be available to oncologists. Scientists have created a drug that blocks the mechanism allowing cancer cells to spread throughout the body. It is expected to make the fight against tumours more effective and increase the likelihood of remission in cancer patients.

Researchers from the oncology center recently announced that they have discovered a new method to combat metastasis. They found that the spread of malignant tumours throughout the body is facilitated by a complex of transcription factors SIX1 and EYA. They developed a drug compound that successfully suppresses this process. The experimental drug was tested on laboratory mice that were implanted with human breast cancer cells, confirming its ability to inhibit the metastasis of this type of tumour.

According to them, some time ago, by scanning a vast database of substances using a specially designed high-throughput molecular screen, they were able to identify compounds potentially capable of blocking the activity of the SIX1 and EYA conglomerate. Since then, scientists have been actively working on creating a new anti-cancer drug based on these compounds. They admit that they do not yet fully understand how it works, but the conducted studies have shown its effectiveness in suppressing the metastasis process.

The protein SIX1 and its corresponding gene, the researchers explain, are involved in mechanisms that ensure rapid proliferation, meaning the reproduction of cells and their migration to other areas. For example, during embryonic development, their expression levels are extremely high. However, in the body of an adult, this transcription factor is practically not synthesized, except for the time of wound healing.

During the malignant transformation of cells, particularly breast cells, it can randomly bind with the EYA protein, which will restart and activate its action. Furthermore, the transcription complex formed by them begins to participate in regulating the frequency of reading and expression of other genes. It modifies signals transmitted through transforming growth factor beta 1 (TGF b), which controls proliferation, cellular differentiation, and other cell functions.

Cells that perceive the TGF b signal undergo epithelial-mesenchymal transition. This is one of the main mechanisms that ensure the plasticity of tumour cells, meaning their ability to respond to changes in their microenvironment and transform in response. Because of this property, they acquire resistance to treatment and the ability to hide from the immune system. All of this leads to the progression of the oncological process and the formation of metastases.

During the so-called epithelial-mesenchymal transition, epithelial cells, which line the surface of the body, including the mucous membranes of internal organs, transform into a mass of mesenchymal cells, similar in properties to stem cells, which can differentiate into various types of cells.

The fact is that epithelial cells do not have the ability to move throughout the body; they must remain in their places – in the tissues from which they originate, because in the absence of their usual microenvironment, they die. This is one form of apoptosis, programmed cell death. Mesenchymal cells, on the other hand, do not have this limitation, so they can freely move throughout the body, forming new cancer foci in different parts. It has long been established that if tumours manage to master the epithelial-mesenchymal transition, metastasis occurs more actively.

In other words, the entire mechanism looks as follows. The protein SIX1 binds with EYA. The “duet” they form initiates the transmission of TGF b signals, which, in turn, activate the epithelial-mesenchymal transition of cells. Cancer cells take advantage of this, acquiring the ability to detach from the primary tumour, “travel” throughout the body, and form new malignant foci, that is, metastasize.

The drug created by the scientists prevents the unfolding of this mechanism by blocking its very first stage – the fusion of transcription factors SIX1 and EYA. In addition, they suspect that the experimental drug somehow also prevents the epithelial-mesenchymal transition in cancer cells, preventing their spread.

“Our experiment lasted three weeks,” says one of the authors of the new method, “that’s how long we administered the drug to the rodents. Nevertheless, observing the animals over the next nine weeks, we found that in the overwhelming majority of them, the tumours did not metastasize. From this, we concluded that the drug compound we developed apparently produces a long-term effect, which we did not suspect.”

Speaking about the safety of the new drug, the scientists note that since SIX1 does not play an important role in the functioning of adult human cells, its suppression should not have negative side effects. “We tested it for toxicity,” say the researchers. “The dose that was twice as high as the one we used during the experiment did not demonstrate pronounced toxicity. This means that the new drug can be used not only as monotherapy but also combined with other anti-cancer methods without the risk of negative health consequences.”

To implement their method, the scientists received several large grants, which, according to them, they intend to use to attract chemists to help refine the compound, making it more stable and effective. They also want to understand exactly how their created drug works, in particular, to understand which molecules it binds to in order to block the binding of SIX1 and EYA. And at the same time, they note: “Our drug successfully suppresses the process of metastasis, and it will allow many cancer patients to avoid the spread of cancer throughout the body and increase the likelihood of remission.”