RESUMO
The pathophysiology of cancer anorexia is complex and serum biomarkers, including growth and differentiation factor(s) (GDF), may be modulated. We explored the association(s) between GDF-15 serum levels and anorexia and, secondarily, with low muscle mass and body weight loss in cancer patients. We considered gastrointestinal and lung cancer patients (CP) and healthy BMI-matched controls. The FAACT-questionnaire was administered to diagnose anorexia and we calculated the L3-SMI by CT scan to assess low muscularity, setting their cutoff values at the lowest tertile. GDF-15 serum levels were assessed by ELISA. We enrolled 59 CP and 30 controls; among CP, 25 were affected by gastrointestinal and 34 by lung cancer. Anorexia was present in 36% of CP. Gastrointestinal CP resulted more anorexic compared to lung CP (p = 0.0067). Low muscle mass was present in 33.9% of CP and L3-SMI was lower in gastrointestinal compared to lung CP (p = 0.049). The GDF-15 levels were higher in CP vs. controls (p = 0.00016), as well as in anorexic vs. non-anorexic CP (p = 0.005) and vs. controls (p < 0.0001). Gastrointestinal CP showed higher GDF-15 levels vs. lung CP (p = 0.0004). No difference was found in GDF-15 between CP with low muscle mass and those with moderate/high muscularity and between patients with body weight loss and those with stable weight. Our data support the involvement of GDF-15 in the pathogenesis of cancer anorexia. The mechanisms of action of GDF-15 in cancer should be further clarified also regarding the changes in muscularity.
RESUMO
Breast cancer is the most commonly diagnosed cancer in women worldwide, and >90% of breast cancer-related deaths are associated with metastasis. Breast cancer spreads preferentially to the lung, brain, bone and liver; termed organ tropism. Current treatment methods for metastatic breast cancer have been ineffective, compounded by the lack of early prognostic/predictive methods to determine which organs are most susceptible to developing metastases. A better understanding of the mechanisms that drive breast cancer metastasis is crucial for identifying novel biomarkers and therapeutic targets. Lung metastasis is of particular concern as it is associated with significant patient morbidity and a mortality rate of 60-70%. This review highlights the current understanding of breast cancer metastasis to the lung, including discussion of potential new treatment approaches for development.
Assuntos
Neoplasias da Mama/genética , Neoplasias Pulmonares/genética , Microambiente Tumoral/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Metástase NeoplásicaRESUMO
Metastasis formation is the leading cause of death in cancer patients. Thus, understanding and targeting this process is an unmet need. Crucial steps during the establishment of metastases include the (pre)metastatic niche formation. This process relies on the interaction of the primary tumor with the environment of distant organs (premetastatic niche) and the interaction of cancer cells with their environment when arriving in a distant organ (metastatic niche). Here, we summarize the current knowledge on the interactions in the tumor environment that result in (pre)metastatic niche formation, specifically in the context of tumor secreted factors, extracellular matrix, immune as well as stromal cells, and nutrient availability. We further highlight strategies to disrupt these interactions as therapeutic interventions against metastases.