Scientists have identified a potential target for treating cancer cachexia, a severe wasting disease. Their research highlights the significant impact that even small groups of brain neurons can have on the body’s response to cancer.
Cancer is a cunning disease that manipulates normal biological processes, such as the immune system, to grow and spread. Elevated levels of Interleukin-6 (IL-6), an immune molecule, by tumors can lead to brain dysfunction in 50%-80% of cancer patients, resulting in cachexia, a life-threatening wasting syndrome, according to Cold Spring Harbor Laboratory (CSHL) Professor Bo Li.
Li explains, “Many cancer patients succumb to cachexia rather than cancer itself. Once a patient reaches this stage, there are limited treatment options available.” However, Li and a team of researchers from CSHL discovered that blocking IL-6 from binding to neurons in a specific brain region called the area postrema (AP) could prevent cachexia in mice, leading to improved health and prolonged lifespan. This breakthrough could pave the way for the development of drugs targeting these neurons to treat cancer cachexia.
In healthy individuals, IL-6 is instrumental in the immune response, signaling the brain when a threat is detected. However, cancer disrupts this process by overproducing IL-6, which binds to neurons in the AP region, causing reduced appetite and contributing to the wasting syndrome.
The researchers employed two approaches to prevent elevated IL-6 from affecting the brain in mice. They first used custom antibodies to neutralize IL-6 and then used CRISPR technology to lower the levels of IL-6 receptors in AP neurons. Intriguingly, both methods yielded similar outcomes: the mice resumed eating, stopped losing weight, and had longer lifespans.
Li was amazed by the profound implications of their findings, stating, “The brain exerts significant control over the body’s physiology. Modifying a small group of brain neurons can have a profound impact on overall health. While I knew there was a connection between tumors and brain function, I didn’t realize the extent of it.”
The research team is now focused on translating these discoveries into treatments for human patients. Collaborations with CSHL researchers Adrian Krainer and Z. Josh Huang could bring them closer to this goal. Li emphasizes the potential benefits of preventing or treating cachexia, stating, “Improving cachexia management could greatly enhance patients’ quality of life and have a widespread positive impact.”
