Cancer wasting is a syndrome of weight loss, loss of appetite, weakness, and anemia. The physical deterioration that accompanies wasting can leave a person weak, tired, unable or unwilling to eat, and with worrisome changes in appearance. These problems can make everyday activities difficult, if not impossible, according to the National Cancer Institute.
It is estimated that up to 80% of people with advanced cancer are wasting, depending on the type of cancer and how patients respond to treatment. Wasting is thought to directly cause up to 30% of cancer deaths, most often due to heart or respiratory failure associated with muscle loss.
“Most people with cancer die from cancerous wasting, not from the cancer,” says Professor Bo Li of Cold Spring Harbor Laboratory in the US, as quoted by EurekAlert. “Once a patient enters this stage, there is no way back because there is basically no cure.”
Is there any glimmer of hope on the horizon to save cancer patients from emaciation?
Wasting and hijacked immune response
Cancer is an insidious disease that hijacks healthy biological processes as it progresses and uses them to grow and spread. For example, it hijacks the body’s immune response and makes it work for it when tumors raise levels of the molecule interleukin 6 (an immune system molecule), which can cause severe brain dysfunction that leads in about 50-80% of cases to cancerous wasting disease.
A glimmer of hope
But Professor Lee and other researchers from four laboratories found that blocking interleukin-6 from binding to neurons in a part of the brain called the area postrema prevented cancerous wasting in mice, and as a result the mice lived longer with healthy brain function. Future drugs that target these neurons could help make cancerous wasting a treatable disease, according to Professor Lee and colleagues’ research published in Nature Communications on July 1.
Interleukin-6 plays a crucial role in the natural immune response. Its molecules are distributed throughout the body and, when faced with a potential threat, alert the brain to coordinate the response. Cancer disrupts this process.
The body produces a large amount of interleukin-6, which begins to bind to neurons in the brain’s area postrema. What cancer does by blocking interleukin-6 “has several consequences,” says Professor Lee. “One is that animals and humans alike stop eating, and another is that it activates a response that leads to wasting syndrome.”
dual approach
The research team took a dual approach to blocking elevated IL-6 from reaching the brain in mice. Their first strategy was to neutralize IL-6 molecules with a custom antibody, and the second was to significantly reduce levels of IL-6 receptors in neurons in the area postrema. Both tactics produced the same results: The mice started eating again, stopped losing weight, and lived longer.
For Professor Lee, the effects were astonishing. “The brain is so powerful at regulating the peripheral system that simply changing a few neurons in the brain has a profound effect on the functioning of the entire body,” he said. “I knew there was an interaction between tumors and brain function, but not to this extent.”
Lee adds that his team is now determined to figure out how to translate this discovery to patients. “If we can use what we’ve learned to prevent or treat cancer wasting, we can dramatically improve patients’ quality of life, and that could have a huge impact on many people’s lives one day.”