Glioblastoma multiforme (GBM) is the most common malignant brain tumor and one of the deadliest cancers. Individuals diagnosed with GBM often have less than 15 months to live due to high proliferation and cell heterogeneity. For high proliferation to occur, telomeres need to exceed their minimum length. This research targets telomeres by inhibiting TRF1, a shelterin protein that binds to the TTAGGG region of the telomere. This is anticipated to stimulate telomere uncapping in all tumor cells. More importantly and unlike telomerase inhibitors, the success of TRF1 inhibition is independent of the telomere’s length which is key in knowing tumors are heterogeneous in regards to the telomere’s length. As a result, TRF1 is not limited to affecting the cell’s viability when telomeres are short. Furthermore, TRF1 is enriched in pluripotent and adult stem cells. This abundance of TRF1 is vital for maintaining homeostasis and pluripotency, suggesting inhibiting it could impair tumor initiation in GBM. Overall, there is a therapeutic window with using TRF1 inhibition with the results leading to increased DNA damage in telomeres, decreased cell stemness, and lowered proliferation in GBM.
Glioblastoma multiforme (GBM) is a common and deadly brain tumor. Due to its high proliferation and cell heterogeneity, individuals diagnosed with GBM often have less than 15 months to live. This research examines the effects of inhibiting TRF1 protein with the goal of preventing the initiation and progression of GBM in mouse models and patient-derived xenografts.