Potential Research Questions
Can cancer be predicted?
Will my patient respond better to immunotherapy, a VEGF inhibitor, or a PI3K inhibitor?
Which nutritional advice should patients be given?
Status Quo and Medical Need
Cancer does not typically occur in an otherwise healthy organisms. Every major cancer type has been associated with obesity and diabetes, and estimates indicate that one third of cancers could be prevented with the suitable lifestyle. Increasing evidence suggests that metabolic deregulation may occur many years before a cancer diagnosis.
Cancer treatments have made remarkable progress, with many new treatment options having come available. However, in spite of companion diagnostics being available in many cases, non-response rates remain high, and there are no positive predictors of response available. Metabolic biomarkers may help personalize treatments, so that they can provide the maximum benefit to patients.
Relevant Metabolite Classes
- Biogenic amines, especially originating from ornithine (putrescine, spermine, spermidine) may define survival through interfering with cell cycle control.
- Amino acids are critically involved in immune modulatory pathways such as IDO and mTOR.
- Glutamine is a major energy source of cancers. Serine and glycine, the latter having been proposed as a prediabetes marker, link increased glycolysis to nucleotide metabolism.
- Mitochondrial dysfunction is probably involved in the pathogenesis of many cancers.
- Some cancers increasingly rely on fatty acid oxidation as an energy source.
Phospho- and sphingolipids:
- Lipids are important mediators of inflammation, which is believed to be a major reason for the association between obesity and diabetes with a number of cancers.
- Lipid metabolism has been shown to be able to assess both cancer risk in healthy individuals, and survival in cancer patients.
- Bile acids are well known to play a role in the pathogenesis of gastrointestinal cancers,
- Bile acids modulate immunity, one of the most promising concepts in cancer therapy.
- Bakiri et al.: Liver carcinogenesis by FOS-dependent inflammation and cholesterol dysregulation; The Journal of Experimental Medicine 2017
- Wu et al.: Serum lipid alterations identified in chronic hepatitis B, hepatitis B virus-associated cirrhosis and carcinoma patients; Scientific Reports 2017
- Ang et al.: Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation; Molecular Cancer Therapies 2016
- Bachmayr-Heyda et al.: Integrative Systemic and Local Metabolomics with Impact on Survival in High Grade Serous Ovarian Cancer; Clinical cancer research 2016
- Brunelli et al.: Comparative metabolomics profiling of isogenic KRAS wild type and mutant NSCLC cells in vitro and in vivo; Scientific Reports 2016
- Fontana et al.: Development of a metabolites risk score for one-year mortality risk prediction in pancreatic adenocarcinoma patients; Oncotarget 2016
- Miolo et al.: Phamacometabolomics study identifies circulating spermidine and tryptophan as potential biomarkers associated with the complete pathological response to trastuzumab-paclitaxel neoadjuvant therapy in HER-2 positive breast cancer; Oncotarget 2016
- Belcheva et al.: Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells; Cell 2014
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For Research Use Only. Not for use in diagnostic procedures.