ABSTRACT
PURPOSE: Growth differentiation factor-15 (GDF-15) is one of the key cachexia-inducing factors. Clinical trials on therapies targeting GDF-15 for cancer and cancer cachexia are underway. While the role of circulating GDF-15 in cachexia has been clarified, the effects of GDF-15 expression within cancer cells remain to be fully elucidated. Hence, the objective of this study was to investigate the expression of GDF-15 in advanced lung cancer tissues and to understand its role in cachexia. METHODS: We retrospectively examined the expression level of full-length GDF-15 in advanced non-small cell lung cancer tissues and analyzed the relationship between the staining intensity and clinical data in 53 samples. RESULTS: We found that 52.8% of the total samples were GDF-15 positive, and GDF-15 expression significantly correlated with improved C-reactive protein/albumin ratio (p = 0.008). It did not correlate with the existence of cancer cachexia and overall survival (p = 0.43). CONCLUSION: Our findings show that GDF-15 expression significantly correlated with improved C-reactive protein/albumin ratio, but not the existence of cancer cachexia in advanced NSCLC patients.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/complications , Lung Neoplasms/complications , Cachexia/etiology , Growth Differentiation Factor 15 , C-Reactive Protein/metabolism , Retrospective StudiesABSTRACT
Background and Objective: Cancer cachexia presents with weight loss, anorexia, and fatigue and worsens the prognosis and quality of life of cancer patients. We aimed to summarize the current relevant discourse in the literature about cancer cachexia in the setting of non-small cell lung carcinoma and the possible current and future treatments. Methods: We conduct a narrative review of the literature on the landscape of cancer cachexia in the context of non-small cell lung cancer, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances. Key Content and Findings: The need for appropriate intervention for cancer cachexia is increasing as the prognosis of patients with advanced non-small cell lung cancer is improving with advances in treatment. Tumor cells play a role in the pathogenesis of cachexia, where they release factors that elicit the production of inflammatory cytokines by the immune system resulting in decreased appetite, abnormal energy metabolism, and skeletal muscle degeneration. Comorbid chronic lung diseases are associated with pulmonary cachexia and sarcopenia and commonly occur in the context of lung cancer, further contributing to the increased incidence of cachexia in patients with lung cancer. Currently, a ghrelin-like agonist, anamorelin, is approved for the treatment of cancer cachexia and is used in clinical practice in Japan. The role that nutritional and exercise therapies can play as added treatments must be further explored. Conclusions: Cancer cachexia remains a poorly understood phenomenon, and awareness must be raised through educational activities for health care providers and patient family members. In addition, new therapeutics targeting cancer cachexia, such as GDF-15 antibodies, are in development, and further progress is expected.
ABSTRACT
Cancer cachexia(CC)is defined as a multifactorial syndrome that causes anorexia and an ongoing loss of skeletal muscle mass(with or without loss of fat mass). In 2011, the definition of CC was established and in 2021, the novel anti-CC drug, anamorelin was launched in Japan. A new era of CC treatment has begun. However, although anamorelin alone has been shown to increase appetite and lean body mass, it has not been shown to restore skeletal muscle function. Therefore, combined intervention therapy that combines nutrition and exercise interventions is required. Those non-pharmacologic therapy are not yet established, but clinical trials are currently underway in Japan or European countries. Further work on CC is underway to elucidate the mechanisms, establish biomarkers, develop new pharmacotherapies targeting the markers, establish new diagnostic and pathological assessment methods, and establish predictors of the efficacy of anamorelin.