Abstract
Muscle cachexia is one of the most critical unmet medical needs. Identifying the molecular background of cancer-induced muscle loss revealed a promising possibility of new therapeutic targets and new drug development. In this review, we will define the signal transducer and activator of transcription 3 (STAT3) protein’s role in the tumor formation process and summarize the role of STAT3 in skeletal muscle cachexia. Finally, we will discuss a vast therapeutic potential for the STAT3-inhibiting single-agent treatment innovation that, as the desired outcome, could block tumor growth and generally prevent muscle cachexia.
Highlights
Muscle cachexia is one of the most common and severe symptoms of advanced cancer, often observed in the course of upper gastrointestinal tract cancers, head and neck cancers, lung cancer, and non-Hodgkin’s lymphomas [1,2]
The leading role is attributed to substances with cachectic activity produced by cancer cells and the immune system, mainly cytokines, including the vital interleukin 6 (IL-6) and others, such as TNF-α, IL-1, IFN-γ, lipolysis activating factor (LMF), and proteolysis inducing factor (PIF) [6,7]
Numerous studies indicate the critical role of signal transducer and activator of transcription 3 (STAT3) activity in skeletal muscle pathology development like muscle cachexia [31]
Summary
Muscle cachexia is one of the most common and severe symptoms of advanced cancer, often observed in the course of upper gastrointestinal tract cancers (especially pancreatic, stomach, and esophageal cancers), head and neck cancers, lung cancer, and non-Hodgkin’s lymphomas [1,2]. Several studies showed that depending on the type of cancer, loss of muscle mass affects 30 to 80% of patients and is responsible for a drastic reduction in quality of life, as well as reducing the effectiveness of chemotherapy, often being the direct cause of death [4,5]. Progressive cancer cachexia syndrome leads to multi-directional changes, affecting all aspect of patients’ wellness, including anemia, nutritional deficiencies, loss of muscle mass and activity limitation, impairment of internal organs and immune system function, changes in external appearance, depression, weakening social bonds, deterioration of quality of life and, as a consequence, faster death of the patient [9]. While significant development of molecular biology, treatment strategies, and novel drugs dedicated to treating several oncological diseases has been introduced, there is still no significant progress in pancreatic cancer therapy, in almost all cases, associated with muscle cachexia. Improvement of muscle hypertrophy and strength, aerobic performance, resistance to fatigue, and regenerative capacity critical illness, cancer cachexia
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