Australian researchers have identified a critical mechanism driving the growth and spread of glioblastoma – one of the most aggressive and deadly forms of brain cancer – potentially paving the way for more effective treatments. This discovery offers a recent avenue for tackling a cancer known for its resistance to conventional therapies and poor patient outcomes.
In a new study conducted by scientists at the University of Adelaide’s Centre for Cancer Biology (CCB), researchers pinpointed the previously unrecognized role of a protein called CD47 in promoting tumor progression, independent of its known function in helping cancer evade the immune system. The research, published today in PNAS, could significantly alter treatment strategies for this devastating disease.
Glioblastoma is exceptionally difficult to treat, with most patients surviving less than 18 months after diagnosis. Current treatments – including surgery, radiation therapy, and chemotherapy – offer limited benefits, and the cancer almost invariably returns.
The new research demonstrates that CD47, already a target of experimental cancer immunotherapies, similarly plays a direct role inside tumor cells, helping them develop, move, and invade surrounding brain tissue. Researchers found that CD47 is particularly abundant at the invasive edges of glioblastoma tumors – the areas responsible for spreading cancer into healthy brain tissue.
“We’ve known for some time that CD47 acts as a sort of ‘do not eat me’ signal, helping cancer cells hide from the immune system,” said Dr. Nirmal Robinson, the study’s lead author. “What we’ve discovered is that CD47 does much more than that; it actually boosts the cancer’s ability to spread and grow.”
Patients with higher levels of CD47 experienced significantly lower survival rates, according to the study. In collaboration with Professor Stuart Pitson’s CCB team, the researchers used a combination of laboratory experiments and animal models to demonstrate that eliminating or blocking CD47 substantially reduced tumor cell proliferation, migration, and invasion.
Tumors lacking CD47 grew more slowly, and in some cases, survival time in the models nearly doubled. These effects occurred even without the presence of immune cells, confirming that CD47 plays a powerful tumor-promoting role beyond immune evasion.
The team also identified a key partner protein called ROBO2, which acts downstream of CD47 and contributes to glioblastoma growth and spread. They found that CD47 protects ROBO2 from degradation inside the cell by sequestering a protein called ITCH, which would otherwise mark ROBO2 for destruction.
“Essentially, CD47 shields ROBO2, allowing it to accumulate and fuel tumor progression,” explained Dr. Ruhi Polara, who co-led the research with Dr. Robinson. “When we remove CD47, ROBO2 is degraded, and cancer cells lose their ability to grow and invade effectively.”
The findings reveal a previously unknown molecular pathway – CD47-ITCH-ROBO2 – that controls glioblastoma cell behavior. This opens new possibilities for treatment strategies that go beyond current approaches.
While therapies targeting CD47 are already being tested in clinical trials for other cancers, they have shown limited success in glioblastoma so far. This new research suggests that directly targeting the CD47-ROBO2 pathway, or disrupting ROBO2 stabilization, could be a more effective strategy.
“By understanding this mechanism, we now have new targets to explore,” said Dr. Polara. “This could lead to the development of therapies that specifically block the tumor’s ability to spread, which is one of the biggest challenges in treating glioblastoma.”
The study also highlights the importance of looking beyond the immune system when developing cancer treatments. “This work changes how we think about CD47,” said Dr. Robinson. “It’s not just an immune checkpoint; it’s a central regulator of tumor biology in its own right.”
Researchers state that further studies are needed to translate these findings into clinical treatments, but this discovery represents a significant step forward in the fight against one of the most devastating cancers. The research underscores the demand for continued investigation into the complex mechanisms driving glioblastoma progression to improve patient outcomes.
“CD47 stabilizes ROBO2 to regulate glioblastoma progression by preventing itch-mediated ubiquitination” is published in PNAS.
