“Combined Therapy” Promising Approach to Treating Brain Cancer
LONDON (Dispatches) - Scientists say that there is now a two-in-one approach which may help keep brain cancer in check.
Glioblastoma is the most common form of brain cancer and also the most deadly that affects people from around 40 years of age, and most people live for less than 2 years after aggressive therapy. "This is a devastating disease,” says Simona Parrinello of the MRC’s Clinical Sciences Centre, who led the research.
The team demonstrates that targeting just one protein has two effects; it both halts the division of the cancer cells, and stops these cells from spreading through normal tissue, a two-in-one approach.
"Current treatments often fail because the tumors spread throughout the brain, and so can’t be fully removed by surgery. If we can target this spread, it may be possible to make therapies more effective. When we target this one protein we block two key features of the tumor: its ability to divide and its ability to invade. It could be a combined therapy in one,” says Parrinello.
Scientists are not clear exactly how the cancer cells invade the brain in patients with this condition, though they know that one key route is through the space that surrounds blood vessels. It is also known that it’s a critical subset of cancer cells that appears to favor this route. These are called "glioblastoma stem-like cells,” or GSCs, because they behave in a similar way to stem cells in the developing and adult brain.
GSCs are particularly resistant to chemotherapy and radiotherapy. Scientists believe that this, and their ability to invade, could mean it’s these cells that are responsible for the regular recurrence of glioblastoma after initial treatment.
Using a cutting-edge technique called intravital imaging, the team discovered that when healthy cells first develop non-cancerous mutations, blood vessels within the brain keep them in a compartment so that they cannot spread and cause damage. They found that the vessels do this by producing a protein, called ephrin-B2, which appears to immobilize the cells and hold them in place. However, when cells become cancerous GSCs, they are able to override this anti-invasion signal, and escape the compartment. Crucially, Parrinello showed that the GSCs do this by producing their own ephrin-B2, which makes them insensitive to the ephrin-B2 already on the blood vessels.
Glioblastoma is the most common form of brain cancer and also the most deadly that affects people from around 40 years of age, and most people live for less than 2 years after aggressive therapy. "This is a devastating disease,” says Simona Parrinello of the MRC’s Clinical Sciences Centre, who led the research.
The team demonstrates that targeting just one protein has two effects; it both halts the division of the cancer cells, and stops these cells from spreading through normal tissue, a two-in-one approach.
"Current treatments often fail because the tumors spread throughout the brain, and so can’t be fully removed by surgery. If we can target this spread, it may be possible to make therapies more effective. When we target this one protein we block two key features of the tumor: its ability to divide and its ability to invade. It could be a combined therapy in one,” says Parrinello.
Scientists are not clear exactly how the cancer cells invade the brain in patients with this condition, though they know that one key route is through the space that surrounds blood vessels. It is also known that it’s a critical subset of cancer cells that appears to favor this route. These are called "glioblastoma stem-like cells,” or GSCs, because they behave in a similar way to stem cells in the developing and adult brain.
GSCs are particularly resistant to chemotherapy and radiotherapy. Scientists believe that this, and their ability to invade, could mean it’s these cells that are responsible for the regular recurrence of glioblastoma after initial treatment.
Using a cutting-edge technique called intravital imaging, the team discovered that when healthy cells first develop non-cancerous mutations, blood vessels within the brain keep them in a compartment so that they cannot spread and cause damage. They found that the vessels do this by producing a protein, called ephrin-B2, which appears to immobilize the cells and hold them in place. However, when cells become cancerous GSCs, they are able to override this anti-invasion signal, and escape the compartment. Crucially, Parrinello showed that the GSCs do this by producing their own ephrin-B2, which makes them insensitive to the ephrin-B2 already on the blood vessels.