In a first-of-its-kind study scientists have found that the cellular makeup of glioblastoma tumours is more heterogeneous than previously suspected. These findings could deepen our understanding of the tumour and lead to the development of more effective responses to this deadly disease.
The large-scale census of individual cancer cells that make up the tumour has revealed that they are even more diverse than previously suspected. The study was conducted by scientists at the Broad Institute and Massachusetts General Hospital (MGH). It was already known that glioblastoma cells exhibit different mutations in their genome and express genes differently, which makes them drug resistant and results in their recurrence. But until now, the extent of this diversity had not been defined.
However, these researchers adopted a relatively new approach called single-cell transcriptomics, which helped them look at patterns of gene expression in each of the 430 individual cells from the brain tumours of five patients.
Glioblastoma studies thus far had looked at the average expression of genes across millions of cells. Based on the gene expression programme most prevalent in the samples, glioblastoma tumors were (in some cases) categorised into one of the four recognized cancer sub-types.
However, in the latest study scientists for the first time examined gene expression patterns of many individual cells, one at a time. This yielded a finer picture of the tumour’s cellular composition and showed that every glioblastoma tumour is in fact an aggregation of individual cells from multiple cancer sub-types. Also, the distribution of these cells varies from tumour to tumour.
Moreover, cancer cells in these tumours exist in many states. The cells, which probably play a role in the recurrence of the disease even after therapy, look like stem cells. The bulk of the tumour is made up of more mature, differentiated cancer cells. Most significantly, the researchers discovered many cells that exist in a twilight zone between these states. In all probability existing treatments miss many of these sub-populations as they target only the most prevalent cells in the tumor.
“What this means is that each tumor needs to be treated based on the complement of the cellular sub-types it contains – not just the most prevalent one,” said co-senior author and renowned cellular scientist Aviv Regev.
The researchers believe that these findings may guide future investigations and approaches to treatment for glioblastoma, the most common and aggressive form of brain cancer in adults.
“Existing therapies may target 99 percent of the cells, but the tumors always come back. Understanding the cellular landscape can provide a blueprint for evolving therapies that target each of the various sub-populations of cancer cells, and ultimately for tailoring such therapies to individual tumors,” said co-senior author Bradley Bernstein.