Spanish researchers discover how tumor cells alter the brain and manage to spread cancer

Madrid.- Spanish researchers have discovered a mechanism by which tumor cells manage to alter the brain to establish themselves and spread cancer, thus causing metastasis, and have also found that a drug already being used for other indications such as asthma could be useful in stopping this process. A team of researchers from the Spanish National Cancer Research Centre (CNIO) led by scientist Manuel Valiente and with Laura Álvaro-Espinosa as the first author of the work, which was published today in the journal Cancer Research, has achieved this, the CNIO reported today in a press release, in which they emphasize that the researchers aim to start a clinical trial in the medium term to test the results.

Normally, when cancerous cells reach the brain they have almost no tools to survive and most are eliminated, but some do manage to alter the brain and “hijack” the cells that should be in charge of defending it (the so-called macrophages and microglia), and instead of fighting the tumor, those defenses are reprogrammed and work in favor of the cancer.

The tumor cells produce a protein (called MIF) that functions as a master key; that key is inserted into a “lock” (a molecular structure called CD74) that is on the surface of the defensive cells, causing them to change their behavior and become allies of the tumor. We recommend reading:

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But researchers have discovered that there is already a drug (ibudilast) that is approved and being used in other countries to treat asthma, which is capable of blocking the union between the key and the lock, and when administered in animal models, researchers have discovered that it managed to stop brain metastasis. The CNIO has valued the importance of the discovery, as approximately 30 percent of cancer patients (especially those with breast, lung, skin, colon, and rectum cancer) end up developing metastasis in the brain, and it is currently an unmet medical need because there are no specific treatments, beyond radiotherapy and surgery. Scientists have also observed that this same mechanism (the alteration of CD74 cells) is also present in neurodegenerative diseases such as Alzheimer’s or multiple sclerosis, so this discovery could open the doors to also treat these pathologies in the future.

Although most tumor cells are eliminated upon reaching the brain, a few do possess the necessary skills to reshape the brain and adapt it to their liking, the CNIO has pointed out in the note it released today, and specified that they begin to change the tissue, to activate molecular pathways that should have been turned off “and to create an environment that is only welcoming to them”, which allows them to proliferate without control and reproduce the tumor.

The drug that researchers have tested, which is already approved as a treatment for asthma in some countries, penetrates the brain well and is well tolerated, and they have verified its results in both animal models and fresh samples from patients derived from different primary tumors. You can also read: The finding, according to the CNIO, is further proof of the value of two major achievements driven by this research center: the creation of the first global bank of living brain metastasis samples (RENACER); and the platform for testing drugs that these samples have allowed to develop (METPlatform). Both resources, the repository and the platform, are innovative research tools highly valued by the international neuro-oncology community, and have already led to several clinical trials currently underway, the center has reported.