A new research project at the Royal College of Surgeons in Ireland shouldmake cancer treatments much more effective, writes Emma Napper
Most deaths from cancer are not caused by the original tumour, but by secondary cancers that spread around the body. Secondary tumours are more difficult to treat than primary tumours, as they don't respond well to normal cancer treatments.
Scientists now think that this may be because the cancer cells are protected by a defence chemical that makes them super-resistant to chemotherapy and radiotherapy. Dr Judith Harmey and her team at the Royal College of Surgeons, Ireland, have been studying how chemicals found in the body could protect tumours.
Her group has just been awarded a €22,000 grant to develop molecules that could block the defence mechanism used by these tough tumour cells. Harmey hopes this could lead to better treatment for secondary cancers.
"At the moment, cancer is primarily treated by surgical removal of the tumour plus chemotherapy and radiotherapy," explains Harmey. Chemotherapy and radiotherapy work by damaging the cancer cell so much that it commits suicide. As more cancer cells die, the tumour becomes smaller. "This is quite effective against the primary tumour but secondary tumours are resistant to these therapies," she explains. Harmey believes that when secondary cancer cells are targeted by chemotherapy and radiotherapy, a first round of them are killed, but the remaining cancer cells fight back by releasing a substance called Vascular Endothelial Growth Factor (VEGF), which stops the treatment from working.
Scientists already know that VEGF is important in the growth and spread of cancer. It works by encouraging new blood vessels to grow around the tumour. These fresh blood vessels then provide the nutrients for the cancer cells to grow and also allow them to spread to other areas.
However Harmey and her team also found that VEGF stops cancer cells from killing themselves, even when they are damaged by chemotherapy and radiotherapy. This earlier work, carried out with money from the Health Research Board and the Higher Education Authority, showed that VEGF "regulates cell suicide" as well as controlling blood vessel growth. "VEGF is central to both processes and targeting it should have a double effect," says Harmey.
Chemicals called VEGF inhibitors can control this substance, and Harmey and her team have shown in lab trials that treating cancer with VEGF inhibitors along with chemotherapy and radiotherapy is "hugely effective" when tackling the cancer growth.
"The future will be a combination therapy," says Harmey. Hitting secondary cancers with chemotherapy, radiotherapy and VEGF inhibitors should knock out their defences and make them easier to treat. "We have still got to prove that what we would see in patients would be the same as in the lab," she said, but she is hopeful that this will be "a clinical reality in the future".
Harmey's next task is to develop effective VEGF inhibitors using the new grant from the Royal College of Surgeons in Ireland. She is studying the potential of a set of chemicals called "peptides" that work by stopping VEGF from reaching the tumour cell. VEGF molecules bind to connection sites on the outside of the cancer cells, and when they attach they tell the cancer cells not to die. The peptides will work by blocking these binding sites, so the VEGF can't protect the tumour. This should make any subsequent chemotherapy or radiotherapy much more effective.
Some VEGF inhibitors do already exist but they are difficult to make and to deliver to patients. Harmey hopes that her peptides will be quick to make and easier to use. Her research will be carried out with surgeons at Beaumont Hospital to ensure that the drugs are medically practical as well as scientifically sound.
"We will come at the problem from both a clinical and scientific perspective. Then the scientists are more aware of the clinical realities of what they are working on," she says.
Emma Napper is a research scientist participating in the British Association for the Advancement of Science Media Fellow programme