With blood samples, they discover why there are cancer patients resistant to radiotherapy

Treated patients not only suffer from side effects, but later manifest the reappearance of tumors.

An blood test. That is enough to identify patients resistant to radiotherapy with brain metastasisaccording to research led by Spanish scientists that has also identified the mechanism that causes this resistance and has found a drug that could be used to reverse the situation.

The description of the findings are published this Monday in the journal “Nature Medicine”, in an article led by researchers from the Spanish National Cancer Research Center (CNIO) and in which the authors propose a new strategy so that patients with brain metastases who would not respond to radiotherapy can benefit from it.

“We are very happy because we have, in a way, a triple result”, explains Manuel Valiente, head of the Brain Metastasis Group at the CNIO, in a statement: with this work “we are beginning to understand the molecular mechanisms of the endurance to radiotherapy; we stratified the patients, so that we could personalize therapy, and we found a drug that eliminates resistance.”

A quarter of people with cancer are in risk of having brain metastases, a type of difficult injury to treat with drugs because the barrier hematoencephalic It acts as an obstacle for the entry of drugs into the brain. Radiotherapy is one of the most used tools to treat metastasis, which mostly develops from primary tumors lung, breast and melanoma.

However, the side effects of treatment can be important and the recurrence of tumors is also frequent.

For this reason, the Valiente team set out to study this resistance. He did it in animal models and in three-dimensional cell cultures of brain metastases from patients, which simulate the tumor tissue. In addition, he analyzed numerous data from cohorts of people with lung, breast, and skin cancer with brain metastases.

The researchers were able to identify a molecular pathway involved in the appearance of resistance and, in particular, a S100A9 protein which functions as an indicator of sensitivity to radiotherapy: the greater the presence of this protein, the more resistance.

The surprise was to verify that this protein can be detected in blood: just a analysis to identify patients resistant to said treatment.

One of the hopeful things, indicates the CNIO, is that a inhibitor drug of the molecule to which S100A9 binds to Activate the resistance; in human clinical trials in phase III (the last) against the Alzheimer’s its safety has been proven.

Likewise, Valiente explains to Efe, it has been found that the drug is capable of cross the blood-brain barrier and reach the brain: “this generates a opportunity unique, as the drug is being tested with another pathology, there is already a long way to go”.

But before reaching a clinical trial for brain metastases, other steps must be taken. In this work, the researchers demonstrate in animal models and in cultures made from samples of patients that the drug could be used to get that resistant people respond to radiotherapy.

They have done the latter thanks to METPlatform, a system that allows investigate with patient samples in a real context, in which the metastatic cells they grow in the tumor microenvironment that surrounds them, in this case the brain.

Once fresh or “live” brain tissue samples are received from hospitals affectedare processed with a simple methodology that It allows its cultivation for a few days. The METPlatform screening technique is applied to these cultures, which analyzes the behavior of hundreds of compounds simultaneously.

In this case, the team chose the drug being tested for Alzheimer’s. In samples of knitting cerebral of seven patients, applied radiotherapy and, seeing that they did not respondcombined it with the aforementioned medication: all were sensitive.

Now the researchers are designing the next step, an observational clinical trial with about 200 patients to verify that the protein S100A9 serves as a biomarker to establish the endurance to radiotherapy and that a blood test detects it.

The last step will be a test to test in people with brain metastases the drug that is now being testing for Alzheimer’s.

According to the CNIO, these S100A9 receptor inhibitors could also serve to reduce the dose of radiation needed to remove the cells tumorousminimizing the effects of irradiation on normal brain tissue and increasing the benefits.

“This study is an example of how, with research that starts in the laboratory we are able to generate a opportunity that can change how radiotherapy is being given in brain metastases”, concludes Valiente.