Cancer cachexia (CC) is a debilitating syndrome that affects 50–80% of cancer patients, varying in incidence by cancer type and significantly diminishing their quality of life. This multifactorial syndrome is characterized by muscle and fat loss, systemic inflammation, and metabolic imbalance. Extracellular vesicles (EVs), including exosomes and microvesicles, play a crucial role in the progression of CC. These vesicles, produced by cancer cells and others within the tumor environment, facilitate intercellular communication by transferring proteins, lipids, and nucleic acids. A comprehensive review of the literature from databases such as PubMed, Scopus, and Web of Science reveals insights into the formation, release, and uptake of EVs in CC, underscoring their potential as diagnostic and prognostic biomarkers. The review also explores therapeutic strategies targeting EVs, which include modifying their release and content, utilizing them for drug delivery, genetically altering their contents, and inhibiting key cachexia pathways. Understanding the role of EVs in CC opens new avenues for diagnostic and therapeutic approaches, potentially mitigating the syndrome’s impact on patient survival and quality of life.

Cancer cachexia is a complex, multifactorial syndrome characterized by severe weight loss, muscle wasting, and systemic inflammation, significantly contributing to cancer-related morbidity and mortality. Signal transducer and activator of transcription 3 (STAT3) has emerged as a central mediator in the pathogenesis of this multifactorial condition. STAT3 regulates a broad range of cellular processes including inflammation, proteolysis, and mitochondrial dysfunction across multiple tissues, particularly skeletal muscle and adipose tissue. Persistent activation of STAT3 in response to tumor-derived and host-derived cytokines drives catabolic signaling cascades, disrupts anabolic pathways, and impairs energy homeostasis. Recent studies have illuminated the cross-talk between STAT3 and other signaling pathways that exacerbate cachexia-related metabolic imbalances. These findings position STAT3 not only as a critical mediator of cachexia progression but also as a promising therapeutic target. Pharmacological inhibition of STAT3 signaling has demonstrated efficacy in preclinical models, offering potential avenues for clinical intervention. This review provides a comprehensive overview of the molecular mechanisms by which STAT3 contributes to cancer cachexia and discusses emerging therapeutic strategies aimed at modulating STAT3 activity to mitigate the progression of this debilitating syndrome.

Cancer cachexia is a multifactorial metabolic syndrome marked by progressive skeletal muscle wasting, systemic inflammation, reduced quality of life, and p

Cancer cachexia is a multifactorial metabolic syndrome characterized by progressive skeletal muscle wasting, chronic systemic inflammation, and profound metabolic imbalance. Sustained activation of the nuclear factor κB (NF-κB) signaling pathway lies at the core of its pathogenesis, driving muscle proteolysis, impairing regenerative capacity, disrupting adipose tissue homeostasis, and promoting insulin resistance and anorexia. By transcriptionally regulating catabolic and pro-inflammatory gene programs across skeletal muscle, adipose tissue, the liver, and the central nervous system, NF-κB establishes a self-amplifying inflammatory–metabolic loop that perpetuates tissue wasting and systemic dysfunction. Accumulating preclinical and clinical evidence identifies NF-κB as a viable therapeutic target in cancer cachexia. Pharmacologic inhibitors (e.g., SR12343, DHMEQ), anti-inflammatory strategies (e.g., nonsteroidal anti-inflammatory drugs and IL-6 receptor–targeting antibodies), and nutritional interventions (e.g., omega-3 fatty acids) have shown efficacy in attenuating cachexia-associated inflammation, metabolic dysregulation, and tissue loss. Notably, emerging multimodal approaches integrating NF-κB modulation with metabolic support, chemotherapy, and behavioral interventions demonstrate synergistic benefits. This review integrates current mechanistic insights and therapeutic advances, highlighting NF-κB as a central pathogenic axis and a compelling target for translational intervention in cancer cachexia.