Researchers at the Spanish National Cancer Research Centre (CNIO) in Madrid have discovered a previously unknown phase in the development of brain metastases. Cancer cells are particularly vulnerable at this early stage. Tests involving three drugs now point to a potential way to combat metastases before they cause symptoms.
Spain Expat Press Editorial Team
by Marlon Gallego Bosbach
Brain metastases are among the most serious consequences of cancer. They develop when cancer cells break away from the primary tumor and travel through the body to the brain. A new study by the Centro Nacional de Investigaciones Oncológicas (CNIO) in Madrid focuses precisely on this early stage.
The team led by Manuel Valiente, head of the Brain Metastasis Research Group, has discovered a previously unknown phase that cancer cells undergo after arriving in the brain. In the long term, the findings could help prevent metastases or reduce the risk of recurrence following surgery. The study was published in the journal Cancer Cell.
Cancer cells initially enter a kind of resting phase
When cancer cells from a lung, breast, or skin tumor reach the brain, for example, they encounter a completely different environment. Many of the cells do not survive this transition.
However, some of the cancer cells manage to adapt to the new environment. Initially, they do not immediately transition into rapid growth; instead, they enter a phase that researchers term a “proliferative pause.”
In this state, the cells temporarily suspend their aggressive behavior and focus on surviving the challenging conditions within the brain. It was precisely this phase that proved to be particularly vulnerable in the studies.
Three drugs show an effect
The researchers investigated the molecular processes occurring within the cancer cells during this early phase. In doing so, they identified targets against which drugs already exist.
Subsequently, the team tested three active compounds in various animal models. According to the CNIO, the drugs were able to eliminate the still-tiny micrometastases before they could develop into larger, clinically detectable metastases. Two of the three drugs tested are already approved for other medical applications.
The researchers were also able to verify the results using human tissue samples. Consequently, the findings are not based solely on observations from animal experiments.
Micrometastases remain invisible so far
However, there is one crucial limitation: medicine cannot currently reliably detect such tiny metastases. The micrometastases studied by the researchers are so small that they cannot be reliably detected using currently available diagnostic methods.
Suitable biomarkers that would allow for the reliable identification of patients at risk are also currently lacking. Consequently, the results cannot yet be directly translated into preventive treatment.
Rather, the discovery opens up a new field of research: if it becomes possible in the future to determine which patients develop such early metastases and when they are particularly vulnerable, drugs could potentially be administered at a stage when the disease is not yet causing symptoms.
Relapses following surgery could also be prevented
This discovery is significant not only regarding the initial formation of brain metastases. The researchers also examined existing metastases. They found that certain molecular processes characteristic of the early metastatic phase also occur at the so-called invasive edges of established metastases. There, cancer cells continue to spread—for instance, by attaching themselves to blood vessels.
According to the researchers, the drugs that were effective against the early growth phase were also able to affect these invasive areas of human metastases. This points to a potential new strategy for preventing recurrence after surgery.
Research has been underway for more than six years
The study was led by Manuel Valiente and lasted more than six years. It involved more than 70 scientists from around 20 research institutions in Spain, the UK, Germany, France, and the USA.
The British PEACE consortium, among others, played a key role in the study of human micrometastases. It makes tumor samples from deceased patients available for research purposes. Autopsies make it possible to detect metastases that had gone undiagnosed during the patients’ lifetimes due to their small size.
In addition, the researchers utilized the Spanish RENACER network, which collects patient samples from neurosurgical procedures. This enabled them to compare the findings from early micrometastases with tissue from fully developed brain metastases.
Clinical trials are to follow
For patients, the discovery does not yet translate into a new treatment option. As a next step, the CNIO aims to determine which combination of the drugs studied offers the greatest therapeutic benefit.
At the same time, scientists are working on biomarkers that could potentially be used in the future to identify micrometastases that currently go undetected. In the medium term, clinical trials are intended to determine whether the drugs are indeed capable of preventing the development of brain metastases or their recurrence following surgery.
A possible new avenue in cancer research
The researchers therefore view their discovery primarily as a new approach in the fight against metastatic cancer. Instead of treating a metastasis that has already developed, it might in the future be possible to attack the cancer cells while they are still in the process of initially adapting to a new organ.
However, whether this approach actually works in patients remains to be proven in clinical trials.
For Manuel Valiente, however, the discovery represents an important step. It could pave the way for combating metastases at a stage when they do not yet cause symptoms – thereby contributing, in the long term, to the prevention of metastases and recurrences.
