αCT1 peptide sensitizes glioma cells to temozolomide in a glioblastoma organoid platform

Glioblastoma (GBM) is the most common form of brain cancer. Even with aggressive treatment, tumor recurrence is almost universal and patient prognosis is poor because many GBM cell subpopulations, especially the mesenchymal and glioma stem cell populations, are resistant to temozolomide (TMZ), the most commonly used chemotherapeutic in GBM. For this reason, there is an urgent need for the development of new therapies that can more effectively treat GBM. Several recent studies have indicated that high expression of connexin 43 (Cx43) in GBM is associated with poor patient outcomes. It has been hypothesized that inhibition of the Cx43 hemichannels could prevent TMZ efflux and sensitize otherwise resistance cells to the treatment. In this study, we use a three-dimensional organoid model of GBM to demonstrate that combinatorial treatment with TMZ and alpha CT1, a Cx43 mimetic peptide, significantly improves treatment efficacy in certain populations of GBM. Confocal imaging was used to visualize changes in Cx43 expression in response to combinatorial treatment. These results indicate that Cx43 inhibition should be pursued further as an improved treatment for GBM.

Automated summary

Glioblastoma (GBM) is a common and aggressive form of brain cancer with poor prognosis due to resistance to the most commonly used chemotherapy. Recent studies have shown that high expression of connexin 43 (Cx43) in GBM is associated with worse patient outcomes. In this study, researchers used a three-dimensional organoid model to demonstrate that combined treatment with a Cx43 mimetic peptide, alpha CT1, and TMZ significantly improved treatment efficacy for certain populations of GBM. These findings suggest that inhibiting Cx43 could be a promising approach for improving GBM treatment.