The majority of cancer patients with advanced disease experience weight loss, including loss of lean body mass. Severe weight loss is characteristic for cancer cachexia, a condition that significantly impairs functional status and survival. The underlying causes of cachexia are incompletely understood, and currently no therapeutic approach can completely reverse the condition. Autophagy coordinates lysosomal destruction of cytosolic constituents and is systemically induced by starvation. We hypothesized that starvation-mimicking signaling compounds secreted from tumor cells may cause a systemic acceleration of autophagy during cachexia. We found that IL-6 secreted by tumor cells accelerates autophagy in myotubes when complexed with soluble IL-6 receptor (trans-signaling). In lung cancer patients, were cachexia is prevalent, there was a significant correlation between elevated IL-6 expression in the tumor and poor prognosis of the patients. We found evidence for an autophagy-inducing bioactivity in serum from cancer patients and that this is clearly associated with weight loss. Importantly, the autophagy-inducing bioactivity was reduced by interference with IL-6 trans-signaling. Together, our findings suggest that IL-6 trans-signaling may be targeted in cancer cachexia.

Increased concentrations of choline-containing compounds are frequently observed in breast carcinomas, and may serve as biomarkers for both diagnostic and treatment monitoring purposes. However, underlying mechanisms for the abnormal choline metabolism are poorly understood.

Inhibition of O-GlcNAc transferase activity reprograms prostate cancer cell metabolism

One of the central hallmarks of cancer is the rapid and infinite cellular proliferation. In order to cope with increased requirement for building blocks and energy, cancer cells develop abnormal metabolic properties. Detailed assessment of cancer cell metabolism can provide biological information for use in both drug discovery and development of personalized cancer therapy. Analysis of intact tissue using high resolution magic angle spinning (HR MAS) magnetic resonance spectroscopy (MRS) gives qualitative and quantitative metabolite measures with minimal sample preparation. Multivariate statistical methods are important tools for analysis of complex MR data and have in recent years been used for analysis of HR MAS data from intact tissue. HR MAS analysis of intact tissue allows combination of metabolomic data with genomic or proteomic data, and can therefore be used both for exploring the molecular biology of cancer and for clinical improvements in cancer diagnostics, prognostics and treatment planning. In this review, the basic concepts of HR MAS are presented, and its use in characterisation of cancer metabolism is discussed with specific focus on selected pathways such as choline metabolism and glycolysis. The use of HR MAS in analysis of amino acids and lipid metabolism in cancer is also reviewed. Finally, the expected role of HR MAS in metabolic characterisation in the near future is discussed.