UTHealth Houston research shows that targeting a certain enzyme in the muscle could help cancer patients keep their muscle mass and possibly live longer.
Cancer cachexia, also known as cancer-induced muscle wasting, is characterized by the loss of muscle mass. A study led by Yi-Ping Li, PhD, professor in the Department of Integrative Biology and Pharmacology at McGovern Medical School at UTHealth Houston, discovered that an enzyme called UBR2 plays a crucial role in cancer cachexia.
Today, the results were released in the PNAS journal.
“The findings will fill a key gap in understanding how cancer causes muscle mass and function loss,” says senior autho Li.
Cancer cachexia is a late-stage cancer condition that affects around 60% of all cancer patients. Patients with cachexia lose weight due to a progressive decrease of muscle mass, resulting in respiratory and cardiac failure. Cachexia kills over 30% of all cancer patients, making the condition a crucial factor in cancer survival.
Historically, there has been no treatment for cancer cachexia due to a lack of knowledge regarding its causes. Therefore, figuring out the molecular pathways by which cancer induces cachexia has been a major area of research for Li’s lab for the past 20 years.
His lab recently revealed the involvement of the enzyme UBR2 in a series of mouse discoveries. This is the primary enzyme in muscle that searches for and destroys myosin heavy chain subtypes in response to cancer. Myosin heavy chain is a crucial component for maintaining muscular contraction.
Cancer produces an increase in UBR2 in muscle, and inhibiting or eliminating UBR2 protects animals against tumor-induced muscle mass and function loss. By studying cancer patients’ muscles, researchers found that UBR2 is elevated, which is connected with cachexia-related myosin heavy chain loss.
According to Li, this finding has important implications for cancer cachexia therapy in the future.
“We have learned in animal studies that muscle wasting in cancer hosts can be ameliorated by blocking UBR2 increase through repurposing some existing drugs,” he added. “Based on the findings, we plan to conduct clinical trials for the therapy of cancer cachexia.”
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