Activation of WNT5A May Drive Glioblastoma Stem Cell Differentiation and Invasive Growth
Glioblastoma multiforme remains the most common and highly lethal brain cancer, known for its tendency to recur. Researchers at The University of Texas MD Anderson Cancer Center have identified a pathway by which cancer cells aggressively spread and grow in the brain, opening up new possibilities for treatment. Study findings were published by Hu et al in Cell.
“The poor prognosis of glioblastoma relates to the near universal recurrence of tumors, despite robust treatment including surgery, radiotherapy, and chemotherapy,” said Baoli Hu, PhD, senior research scientist at MD Anderson. “Our study shows the potential for a new therapeutic strategy based on targeting the mechanisms allowing glioma to regrow aggressively in the brain.”
Study Findings
Dr. Hu and his colleagues developed a glioblastoma model to locate glioma stem cells, which, like all stem calls, have the ability to become other cell types. The researchers further found that the gene WNT5A, when activated, allowed glioma stem cells to transition, leading to invasive tumor growth.
“We uncovered a process by which glioma stem cells mediated by the WNT5A gene become endothelial-like cells,” said Dr. Hu. “These new cells, known as GdECs, recruit existing endothelial cells to form a niche supporting the growth of invasive glioma cells away from the primary tumor, often leading to satellite lesions and disease recurrence.”
Clinical data revealed higher WNT5A and GdECs expression in these satellite lesions and recurrent tumors than was observed in the primary tumors, affirming the tie between WNT5A-mediated stem cell differentiation and glioma cell spread throughout the brain, and contributing to the cancer’s lethalness.
The study established WNT5A as a key factor in glioma stem cells transitioning to GdECs. The team believes this opens up the possibility for a new therapeutic strategy for patients with glioblastoma.
Recent clinical data show the U.S. Food and Drug Administration-approved drug, bevacizumab (Avastin), did not benefit patients as a first-line treatment of recurrent glioblastoma by targeting vascular endothelial growth factor (VEGF). With this new information, the study team proposes an additional therapeutic approach targeting WNT5A and VEGF signaling pathways for recurrent glioblastoma.
“Our preliminary data show that bevacizumab may increase WNT5A-mediated GdEC differentiation and recruitment of existing endothelial cells, resulting in no proven benefit to patients with glioblastoma,” said Dr. Hu. “This new strategy should improve the outcome of brain cancer patients undergoing VEGF therapy by limiting new tumor growth and invasion and disease recurrence,” said Dr. Hu.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
