tonabersat [Neurosurgery Wiki]

This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong.

Human and mouse breast and lung cancer cells express [[protocadherin 7]] (PCDH7), which promotes the assembly of carcinoma-astrocyte gap junctions composed of [[connexin 43]] (Cx43). Once engaged with the astrocyte gap-junctional network, brain metastatic cancer cells use these channels to transfer the second messenger [[cGAMP]] to astrocytes, activating the STING pathway and production of inflammatory cytokines such as interferon-α (IFNα) and [[tumor necrosis factor]] (TNF). As paracrine signals, these factors activate the STAT1 and NF-κB pathways in brain metastatic cells, thereby supporting tumour growth and chemoresistance. The orally bioavailable modulators of gap junctions [[meclofenamate]] and [[tonabersat]] break this paracrine loop, and we provide proof-of-principle that these drugs could be used to treat established brain metastasis
((Chen Q, Boire A, Jin X, Valiente M, Er EE, Lopez-Soto A, Jacob LS, Patwa R,
Shah H, Xu K, Cross JR, Massagué J. Carcinoma-astrocyte gap junctions promote
brain metastasis by cGAMP transfer. Nature. 2016 May 18;533(7604):493-8. doi:
10.1038/nature18268. PubMed PMID: 27225120; PubMed Central PMCID: PMC5021195.
)).