Tumor Cells Reprogram Brain to Aid Metastasis, Asthma Drug Shows Promise in Blocking Process
Tumor cells are capable of “reprogramming” the brain to favor metastasis, and a drug already approved for asthma could block this process. This is the main conclusion of a new study by the Spanish National Cancer Research Centre (CNIO), published in the journal Cancer Research, which opens new options in the treatment of brain metastasis, a complication that affects almost a third of cancer patients.
For decades, brain metastasis has been considered the terminal phase of the most aggressive tumors, to the point that patients who developed it were excluded from clinical trials due to their poor prognosis. But, the CNIO Brain Metastasis group, led by Manuel Valiente, has been dismantling this premise for more than ten years. His research shows that the success of cancer cells in the brain is not coincidental: it involves an active reprogramming of the brain environment to turn it into a favorable niche for their growth.
“To thrive, tumor cells must alter the brain itself,” explains Valiente according to CNIO. When they reach the central nervous system, most are quickly eliminated, as they lack the necessary tools to survive there. Only a few possess the ability to initiate a true molecular reform of brain tissue. These cells activate pathways that should remain inactive and transform the environment into a space that is uniquely favorable to the tumor.
From Defensive Cells to “Allies” of the Tumor
The new CNIO discovery focuses on a mechanism until now unknown and potentially common to multiple types of cancer that metastasize to the brain. The study, with researcher Laura Álvaro Espinosa as first author, identifies the key role of a protein called MIF (Macrophage Migration Inhibitory Factor). This molecule, produced by tumor cells, functions as a “key” that is normally never used in the brain. Its target is the CD74 receptor, present in macrophages and microglia, the immune cells that should defend the nervous system.
Under normal conditions, these cells would act to stop metastasis. However, MIF manages to reprogram them to work in favor of the tumor. Instead of activating the immune system, CD74-modified macrophages and microglia facilitate the spread of cancer. This conversion of defensive cells into tumor allies constitutes a key step in the progression of the disease.
The most promising thing about the work is that this mechanism can be blocked. The CNIO team has identified a drug, ibudilast, already approved in other countries to treat asthma, which acts precisely preventing the union between MIF and CD74. In animal models and in patient samples, medication administration significantly reduced brain metastasis. The compound easily penetrates the brain and is well tolerated, essential characteristics for a treatment of this type.
Potential Implications Beyond Cancer
The CNIO aspires to launch a medium-term human clinical trial, a crucial step to determine the real effectiveness of the drug in cancer patients. Given the lack of specific therapies – beyond radiotherapy and surgery – this advance represents a new horizon in a field where the clinical necessitate is urgent: it is estimated that 30% of patients with breast, lung, melanoma, colon or rectal cancer develop brain metastases at some point.
The study also suggests that the MIF CD74 mechanism could be involved in other non-tumor neurological pathologies, such as Alzheimer’s or multiple sclerosis, which opens the door to future therapeutic applications beyond cancer.
If trials confirm its effectiveness, ibudilast could turn into the first treatment specifically aimed at stopping brain metastasis, transforming the prognosis of thousands of patients every year.