A pathway has been identified by researchers from The University of Texas MD Anderson Cancer Center (TX, USA), providing a potential mechanism by which glioblatoma multiforme cancer cells grow and spread aggressively in the brain. This study, published recently in Cell, may lead to new possibilities for treatment for the common and highly lethal cancer that is known for its ability to relapse.
“The poor prognosis of glioblastoma relates to the near universal recurrence of tumors despite robust treatment including surgery, radiotherapy and chemotherapy,” stated author Baoli Hu (The University of Texas MD Anderson Cancer Center). “Our study shows the potential for a new therapeutic strategy based on targeting the mechanisms allowing glioma to regrow aggressively in the brain.”
The team located glioma stem cells by developing a glioblastoma model; in this model the researchers discovered that when the WNT5A gene is activated in these stem cells, the glioma stem cells transition, thus contributing to invasive growth of the tumor.
“We uncovered a process by which glioma stem cells mediated by the WNT5A gene become endothelial-like cells,” continued 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, and often leading to satellite “lesions” and disease recurrence.”
Clinical data demonstrated higher levels of WNT5A and GdECs expression within satellite lesions and recurrent tumors as opposed to the levels observed in primary tumors, thus supporting the relationship between WNT5A-mediated stem cell differentiation and glioma call spread across throughout the brain, as well as contributing to glioblastoma’s lethality.
This new information led the team to propose further therapeutic approaches for recurrent glioblastoma by targeting WNT5A and vascular endothelial growth factors (VEGF) pathways. This follows recent clinical data demonstrating that the US FDA-approved bevacizumab did not benefit patients as a first-line treatment of recurrent glioblastoma by targeting the VEGF pathway alone.
“Our preliminary data show that bevacizumab may increase WNT5A-mediated GdECs differentiation and recruitment of existing endothelial cells resulting in no proven benefit to patients with glioblastoma,” said 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,” concluded Hu.