Release date: 2018-06-14
The brain microenvironment puts a particularly severe selection pressure on cancer-initiating cells, but cancer can always avoid these stresses with unknown mechanisms and successfully establish metastases in the brain. Activated astrocytes are a key component of the brain's microenvironment and can limit metastases without entering the lesion.
Image source: CNIO
In order to reveal the mechanism of brain metastase formation, researchers from the National Cancer Center of Spain, led by Dr. Manuel Valiente, found that brain metastatic cells can pass signals from a group of activated astrocytes near the lesion area of ​​the metastases. Signal transducer and activator of transcription 3 (STAT3) activates and maintains pre-metastatic activity. Related research results were published in Nature Medicine, entitled "STAT3 labels a subpopulation of reactive astrocytes required for Brain metastasis".
This group of activated astrocytes can benefit metastatic cancer cells through their regulatory effects on innate immunity and the acquired immune system. In patients, activated STAT3 signaling in activated astrocytes is associated with reduced survival in intracranial metastases. Inhibition of STAT3 signaling in active astrocytes can reduce the probability of brain metastases in various primary cancers, and even advanced cancer models.
The researchers also found that a safe, oral, and STAT3-inhibiting therapy showed significant anticancer effects in advanced cancer patients who had already had brain metastases. The response to this therapy is particularly pronounced in the central nervous system, and even several patients have achieved full response.
Overall, the study found a new treatment for brain metastases, which is expected to significantly improve survival in patients with secondary brain metastases, given the high incidence of brain metastases and mortality.
Reference materials:
Neibla Priego et al, STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis, Nature Medicine (2018). DOI: 10.1038/s41591-018-0044-4
Source: Bio Valley
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