How to lift brain cancers’ cloaking device?
by A Jensen
A team led by Dr. Alvares-Prado and Prof Joyce from the Department of Oncology at Lausanne University have made a step towards our understanding and treatment of glioblastomas (brain cancer), with new research published in Cell Reports entitled ‘Cancer cell and microenvironmental rewiring by ADAR1 loss impairs glioblastoma tumor growth and extends survival’.
Glioblastomas are an aggressive, hard-to-treat form of brain cancer with a 5-year survival rate of around only 5%. Invasive surgery, followed by radiation and chemotherapy are standard routes for treatment, however tumours often recur and become untreatable. The need for new understanding and treatment options for this underserved group is of high priority for patients, brain cancer researchers and clinicians alike.
The team from Lausanne funded in large part by the Brain Tumour Charity Future Leaders Program, have made an important step in this direction, identifying a gene (ADAR1) that plays a role in progression and treatment of glioblastomas, through important interactions of the cancer cells with the immune system.
During the progression of glioblastomas, the immune environment of the brain begins to change, driven by the growing cancer cells and the signals they exert. Typically, immune cells are able to sense non-self-cells and remove them. However, in glioblastoma the cancer cells become ‘invisible’ to the immune system thus able to survive and grow. In this new research ADAR1 was genetically deleted in mouse models of glioblastoma, resulting significant tumour reduction, leading to increased lifespan. This deletion had a dual effect. First, causing the cancer cells to reduce their proliferation, and secondly through the re-programming of the immune cells. The team showed that the immune environment in animals with loss of ADAR1 became ‘pro-inflammatory’ and ‘anti-tumoral’- i.e. the immune cells were once again able to recognise and remove the cancer cells effectively.
To evaluate whether targeting ADAR1 would be a viable treatment option, the researchers then went onto treating human glioblastoma cells with 8-azaadenosine (a small molecule inhibitor of ADAR1), resulting in reduced growth of the cancer cells. While there is still much work to be done in the formulation of drugs such as this that is able to penetrate into the brain successfully, these findings do pave a clear pathway for further investigation as a translational treatment strategy.
Read the full article below!
https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00922-2
