How DNA link could unlock mystery of cancer patients ‘wasting away’
One of the most serious impacts of cancer is the sudden loss of weight, appetite, and muscle that can hit some patients in the later stages of the disease. This wasting syndrome is known as cachexia and it can be triggered in other serious conditions, including heart disease and HIV.
In addition, an inherited version of extreme wasting syndromes can affect children. Known as Cockayne syndrome, it causes them to suffer severe malnutrition and wasting that parallels the effect of cachexia.
“In the case of patients with cancer, individuals can go from seeming quite normal to being wheelchair-bound due to muscle wasting and weight loss in only a matter of a few months,” said oncologist Professor Charlie Swanton, of the Crick Institute in London. “It’s quite frightening.”
Despite considerable scientific effort, cachexia’s causes have remained a mystery. However, recent work by UK researchers has raised hopes that scientists are closing in on some of the causes of this affliction.
A team of scientists led by Professor Ketan Patel, director of the Weatherall Institute of Molecular Medicine in Oxford, has recently linked the disease to DNA damage that disrupts chemical messengers that are sent to the brain, causing it to release appetite-suppressing hormones. The result is severe weight loss.
The researchers found that this process is often initiated when the naturally occurring chemical formaldehyde builds up in a person’s blood stream. When this is filtered by the kidneys, their cells suffer DNA damage in the process. This, in turn, causes their kidneys to secrete a hormone which messages the brain to suppress appetite.
“When you have chemotherapy, you are given a chemical substance that attacks DNA in much the same way as formaldehyde does,” said Patel. “In other words, it may be damaging DNA and triggering these signals that tell the brain to suppress appetite.”
The research also suggests a possible avenue for treating the problem, he added. The messenger sent out by the kidney to the brain is a chemical called GDF15, a discovery that holds important clinical implications.
“It suggests we may be able to treat weight loss in patients undergoing cancer chemotherapy and in children with Cockayne syndrome by administrating an antibody which neutralises GDF15. We might then be able to block these messages and halt the onset of their cachexia.”
However, Swanton counselled caution. “This is a fascinating and important study. GDF15 is one known mechanism that contributes to the development of cachexia but it is not going to be the only one. We need more work like this to understand other routes and causes as a matter of urgency as we know this syndrome contributes to our inability to treat patients as they become weaker.”
Progress in genomics and in understanding the causes of cachexia has led the disease to becoming a focus for the Grand Cancer Challenges programme recently established by Cancer Research UK and the US National Cancer Institute. This pinpoints the condition as a prime target for tumour research on both sides of the Atlantic.
“Cachexia is more than losing your appetite and weight loss, and doctors struggle to reverse this condition when it takes hold,” added Michelle Mitchell, chief executive of Cancer Research UK.
“It is a complex problem that has an enormous impact on people with cancer, damaging their wellbeing and lowering their energy at a time when they need it most.
“Research that can tell us more about the mechanisms behind cachexia is essential if we want to find a way to manage it.”
Source: The Guardian
