Game Changer Grant Awarded to Michelle Monje

Recent research has uncovered that DIPG tumors exploit growth signals from the surrounding normal brain tissue, which supports tumor growth and contributes to its resistance to therapy. A key aspect of this resistance may involve "tumor microtubes" (TMs), thin extensions that form connections between cancer cells. These TMs create a cooperative network that enables cancer cells to communicate, evade therapy, and promote tumor survival, a mechanism previously observed in adult glioblastoma.

Our preliminary studies suggest that similar tumor microtubes are present in DIPG, and we aim to study their role in the tumor's growth, progression, and resistance to treatment. Specifically, we will investigate whether these structures help DIPG resist therapies and explore how disrupting them could improve treatment outcomes.

The proposed research has three main objectives: (1) to identify and characterize the tumor microtube network in DIPG by examining patient-derived cell cultures and animal models to determine their presence and structure across different DIPG subtypes, (2) to investigate the role of specific proteins like neuroligin-3 (NLGN3) in the formation and maintenance of these microtubes, and (3) to evaluate the therapeutic potential of disrupting the tumor microtube network by targeting key proteins such as Connexin-43 (CX43), which is involved in forming these microtube connections. By blocking the formation of TMs, we hypothesize that DIPG cells will become more vulnerable to treatments like panobinostat, a drug that has shown some initial success but is limited by the cancer’s ability to develop resistance.

This research has the potential to reveal a novel therapeutic target in DIPG, paving the way for new strategies to combat this devastating disease.