Exploring Filamin A as a potential therapeutic target in Glioblastoma development and plasticity

Glioblastoma (GBM) is the most common and deadliest type of human primary brain cancers and remains incurable. Tumor recurrence after standard of care treatment is one of the central challenges. Transformed terminally differentiated astrocytes and neurons may revert to a stem cell state, migrate, and establish a recurrent heterogeneous tumor. The process where cells switch from non-stem to cancer stem cell-like cells is referred to as cancer cell plasticity. Filamin A (FlnA) is an actin cross-linking protein that serves as a scaffold and is involved in multiple cell functions, including cell migration and adhesion. FlnA has been implicated in various types of cancer development but its functional role in GBM remains unknown. Previous unpublished in-vitro work in our lab, in human GBM cell lines, showed that FlnA plays an integral role in tumor plasticity. However, the effect of FlnA must be investigated in the context of the malignant microenvironment in-vivo. In this study we aim to investigate how silencing FlnA will change the tumor initiation and plasticity capacity of glioma cells in our murine GBM model. As phenotypic plasticity is considered today one additional component of intra-tumor heterogeneity, we believe that blocking the ability of tumor cells to transition to the more resistant cancer stem cell state may be a better therapeutic approach than conventional treatment of the primary tumor. Therefore, inhibition of FlnA may prove to be an integral therapeutic target.