CANCER CHEMOTHERAPY-INDUCED CACHEXIA: THE ORPHAN DISEASE

Cancer remains a major cause of mortality worldwide, with chemotherapy serving as a cornerstone of cancer treatment. While effective in targeting malignant cells, chemotherapy is associated with debilitating side effects, including cachexia a complex, multifactorial syndrome characterized by unintentional weight loss, muscle wasting, fatigue, and reduced physical function. This condition arises from cancer progression and chemotherapy-induced toxicity, compounded by systemic inflammation, oxidative stress, and mitochondrial dysfunction. Chemotherapy agents trigger the release of pro-inflammatory cytokines, promote the generation of reactive oxygen species, and activate the ubiquitin-proteasome system, all of which contribute to skeletal muscle atrophy. The resulting impairment in physical function, diminished treatment tolerance, and worsened prognosis significantly impact patient outcomes. Unlike general cancer-associated muscle wasting, chemotherapy-induced cachexia involves unique mechanisms, including the activation of nuclear factor kappa beta and mitogen-activated protein kinase pathways by agents such as Cisplatin. Cachexia is further aggravated by side effects such as reduced appetite, nausea, and fatigue, leading to myosteatosis and deterioration in muscle mass and function. Current therapeutic approaches include pharmacological agents such as ghrelin receptor agonists, selective androgen receptor modulators, omega-3 fatty acids, nutritional support, and physical exercise. However, these interventions remain inadequate. Given the central role of mitochondrial dysfunction in muscle wasting, mitoprotective compounds hold promise as targeted therapies. A comprehensive approach integrating pharmacological, nutritional, and exercise-based strategies is essential for effective management. Despite the absence of approved treatments, ongoing research aims to develop novel therapies to preserve muscle mass and enhance the quality of life for cancer patients.