Between 20% and 40% of solid tumors generate brain metastases, which are complex to treat, since they often cannot be eradicated with surgery and, in most cases, chemotherapy fails. That is why the most widely used treatment is radiotherapy. Even so, on some occasions, this tool is also not effective or stops working.
be.
The discovery
You have identified a biomarker that indicates who will respond to radiation therapy
The biologist Cátia Monteiro, who received her doctorate in 2020 in the laboratory of Manuel Valiente, at the National Center for Oncological Research (CNIO) in Madrid and is currently a researcher at the pharmaceutical company MSD, has identified a molecular mechanism or biomarker of resistance to this radiological therapy. This makes it possible to identify which patients will respond and which patients will not to radiotherapy. And for the latter, the researcher has found a drug that makes them sensitive to radiotherapy again.
personalized therapy
With a drug it is possible to reverse resistance to treatment
Why is it difficult to treat brain metastases?
For its characteristics. The brain is protected by the blood-brain barrier, which prevents drugs from reaching brain cells, including cancer cells. And although this is a protective measure, in the case of metastasis it is an inconvenience for treatment. That is why they are mostly treated with radiotherapy.
What primary tumors give rise to brain metastases?
Especially lung, breast and melanoma tumors.
Is radiotherapy efficient to treat them?
It is one of the most used forms of treatment in brain metastases. It is effective in controlling the symptoms associated with the disease and decreases the incidence of intracranial relapses. However, the few existing therapeutic alternatives for this type of patients and the little knowledge about the molecular aspects that could be associated with resistance to radiotherapy made us question whether we could somehow improve the
radiation therapy efficiency.
What have they discovered?
We start from the idea that the molecular study of brain metastasis could give us clues to be able to increase the efficiency of this therapy. We wanted to see if there was any molecular pathway activated that we could modify to eliminate resistance to radiotherapy and make the tumor respond again. For this, we carried out a study in animals and in cultures of tumor tissues derived from patients; we analyzed data from cohorts of patients with breast, melanoma, and lung cancer, and identified a biomarker, S100A9, that allows us to predict who will respond to radiotherapy. This marker makes it possible to do a first screening and only administer radiotherapy to those people who will benefit from it, because it has important side effects on health.
What is that biomarker, S100A9?
It is a protein present both in tumor cells and in their microenvironment and is usually related to inflammatory processes that encourage tumor proliferation. Elevated levels of this protein are correlated with a worse prognosis of response to radiotherapy. This observation has allowed us to classify patients into those who will potentially respond to radiotherapy and those who have a high probability of not responding to treatment. In this way we can personalize the therapy.
As?
After identifying the molecular mechanism of resistance to therapy, we retrospectively analyzed the response of patients who had been treated with radiotherapy. We had access to live tissue samples from those patients and we knew in advance which ones ended up generating resistance. Later, in the laboratory, we verified how, by applying a drug to these samples aimed at blocking the molecular mechanism that we had identified, they became sensitive to radiotherapy again. In addition, we have observed that it is possible to detect this biomarker in blood, which opens the door to performing liquid biopsies when tissue samples are not available.
What implications do your results have?
They allow us to personalize the therapy given to patients and only give radiation therapy to those who are going to respond. It also allows us to try to rescue those who in the long run will end up generating resistance to treatment by applying the drug that we have studied.
When can this discovery be applied in the clinic?
At the moment we are conducting a clinical study with Renacer, the National Brain Metastasis Network, which is in charge of collecting blood samples.
of patients treated with radiotherapy, and we are evaluating
the levels of the biomarker that we have identified and comparing them with the levels of response to radiotherapy. Also
We have a phase I and II clinical trial underway to verify the safety and efficacy of the drug, and confirm whether it is capable of reversing resistance to radiotherapy.
