Gap Junction Inhibitors

Another therapy approach described to target the survival function of the metastatic niche are gap junction inhibitors. In the brain metastatic niche, astrocytes were shown to interact with disseminated tumor cells (DTCs) through gap junctions in order to further their survival through the second messenger cGAMP and the activation of the STING pathway as well as interferon-alpha and tumor necrosis factor (Chen et al. 2016). Therefore, by inhibiting these gap junctions, cancerous cells are not able to utilize surrounding cells to further their survival. Some of these gap junction inhibitors include the FDA-approved tonaberset and meclofenamate. This therapy is useful in halting cell survival but is systemic as many cells throughout the body interact through gap junctions, including those that are healthy. Instead, these gap junction inhibitors may be better utilized in synergy with a more specific treatment to target only cancerous cells.