A new pathway that is used by cancer cells to infiltrate the brain has been discovered by a team of Canadian and American research groups.
The research, led by the Singh Lab at McMaster University, has also revealed a new therapy that shows promise in blocking and killing these tumours.
The findings could lead to the development of news treatments for glioblastoma, the most aggressive form of brain cancer.
With existing treatments like surgery, radiation therapy and chemotherapy, the tumours often return, and patient survival is limited to only a few months.
With this new treatment, the returning cancer cells were destroyed at least 50 per cent of the time in two of the three diseases tested in preclinical animal models.
Sheila Singh, professor with McMaster’s Department of Surgery and director of the Centre for Discovery in Cancer Research, is the study’s co-senior author.
The researcher said: “In glioblastoma, we believe that the tumour hijacks this signalling pathway and uses it to invade and infiltrate the brain.
“If we can block this pathway, the hope is that we can block the invasive spread of glioblastoma and kill tumour cells that cannot be removed surgically.”
To discover the pathway cancer cells use to infiltrate the brain, researchers used large-scale gene editing technology to compare gene dependencies in glioblastoma when it was initially diagnosed and after it returned following standard treatments.
By doing this, researchers discovered a new pathway used for axonal guidance – a signalling axis that helps establish normal brain architecture – that can become overrun by cancer cells.
To stop the invasion of cancer cells, researchers targeted the hijacked signalling pathway using different strategies including a drug developed in John Lazo’s group at the University of Virginia, and also by developing a new therapy using CAR T cells to target the pathway in the brain.
They honed in on a protein called Roundabout Guidance Receptor 1 (ROBO1) that helps guide certain cells, similar to a GPS.
Chirayu Chokshi, a former PhD student who worked alongside Singh at McMaster University, is the study’s lead author.
Chokshi said: “We created a type of cell therapy where cells are taken from a patient, edited and then put back in with a new function.
“In this case, the CAR T cells were genetically edited to have the knowledge and ability to go and find ROBO1 on tumour cells in animal models.”
Singh and Chokshi say the treatment can also apply to other invasive brain cancers.
In the study, researchers examined models for three different types of cancer including adult glioblastoma, adult lung-to-brain metastasis, and paediatric medulloblastoma.
In all three models, treatment led to a doubling of survival time. In two of the three diseases, it led to tumour eradication in at least 50 per cent of the mice.
Singh said: “In this study, we present a new CAR T therapy that is showing very promising preclinical results in multiple malignant brain cancer models, including recurrent glioblastoma.
“We believe our new CAR T therapy is poised for further development and clinical trials.”
