Cancer Cachexia WeightLoss Expalined
It all starts with the tumor. Tumor cells release several inflammatory cytokines—mainly TNF-alpha, IL-1, IL-6, and IL-8. These cytokines circulate throughout the body and trigger a chain reaction that disrupts normal metabolism.
One major target is the skeletal muscle. These cytokines activate pathways that increase proteolysis—meaning the muscle starts breaking down its own proteins. Additionally, there is increased oxidative stress and sometimes nerve damage to muscle fibers. Together, this leads to progressive muscle wasting, which is a hallmark of cancer cachexia. At the same time, these signals also affect adipose tissue. The inflammatory cytokines stimulate lipolysis—the breakdown of fat—and promote ‘WAT browning,’ converting white fat into more metabolically active brown-like fat. This makes the body burn even more energy, leading to rapid loss of fat stores.
The immune system contributes as well. Chronic inflammation maintains high cytokine levels, amplifying muscle and fat loss. So, instead of helping, the immune response actually worsens the process. The gut and microbiome are affected too. Tumors can cause dysbiosis—an imbalance in gut bacteria—and alter hormones like ghrelin, which controls appetite. This leads to anorexia—a medical loss of appetite. Even if nutritional intake improves, the metabolic abnormalities prevent weight gain. The brain gets involved through these inflammatory pathways. It becomes resistant to hunger hormones, so patients feel full quickly, eat less, and their body continues to break down tissues for energy.
Finally, the heart and other organs are affected. Muscle breakdown isn’t limited to skeletal muscle; cardiac muscle can also undergo atrophy, leading to decreased functional capacity and worsening outcomes. In summary, the tumor releases inflammatory signals, which drive muscle breakdown and fat loss. These signals, in turn, reduce appetite, and systemic inflammation sustains the entire process. This creates a vicious cycle that leads to progressive weight loss that cannot be reversed simply by eating more.