Chapter 16: Metabolomics for oncology
by Susan Costantini, Alfredo Budillon
Cancer cells alter their metabolism to maintain cellular proliferation and survival, and require large amounts of nutrients, such as glucose, and energy. Many evidences suggest that also the utilization of amino acids, lipids and nucleotides contributes significantly to cancer cell metabolism. Therefore, this chapter firstly summarizes the main dysregulated metabolic pathway, that support cancer initiation and progression, including glycolysis and Warburg effect, metabolic symbiosis, metabolism of glutamine, serine, methionine and proline, involvement of arginine and ornithine in linking TCA and urea cycles, and lipid and nucleotide synthesis pathways. In the second part of this chapter, we perform a systematic overview of recent metabolomics studies developed by using several techniques (1H-NMR, GC-MS, LC-MS, vibrational and Raman spectroscopy) on different biological matrices such as serum/plasma, urine, tissues, feces, saliva, and others, from cancer patients.
Susan Costantini graduated in Chemistry and achieved the Specialty Certification in Clinical Pathology and Biochemistry at University Federico II of Naples (Italy). She obtained her PhD in Computational Biology at the Second University of Naples and Master’s degree in Environment and Cancer at the University of Sannio. She is a contract professor of Biology, Biochemistry, and Bioinformatics at University Federico II of Naples and Vanvitelli Campania. Since 2008, she has been a researcher at the Mercogliano Laboratory of the National Cancer Institute of Naples ”Pascale Foundation”. She is the author of more than 150 publications (Scopus H-index: 33). Her research activity is currently focused on the study of the cytokinomic and metabolomic/lipidic profile by 1H-NMR and LC-MS in various cellular systems, biological fluids, and tissues of cancer patients. Moreover, her research activities include the application of systems biology approaches to integrate “omics” data by computational and bioinformatics methods.
Dr. Alfredo Budillon graduated in Medicine (1989); PhD in Oncology (1996); Board Certification in Oncology (1997); Master degree in Health Economy, Management and Bioethics (2001); gained experience in biochemistry and antitumor experimental therapeutics as Fogarty visiting fellow at National Cancer Institute, NIH, Bethesda, USA ( 1990 -1995) where he published several papers on the molecular targeting of altered cAMP-dependent protein kinase in cancer models. Dr. Budillon joined Istituto Nazionale Tumori- IRCCS G. Pascale, Napoli, Italy in 1996 where he is currently Director of Experimental Pharmacology Unit and of Laboratory of Pharmacology & Proteomics, being in charge of the 600MHZ-based NMR Metabolomics Facility and responsible of the Animal Facility at Oncology Research Center of Mercogliano (CROM), Italy. He is author of more than 170 publications (H-Index 42) most on the molecular mechanism of novel anticancer drugs, particularly epigenetic drugs, and the potential combination approaches with conventional drugs. Some of these findings were translated into clinical trials particularly rectal and colon cancer patients. Recently he focused his research on targeting metabolic reprogramming in cancer cells, particularly in cancer stem cell compartment. Other scientific interests are related with System Biology approach and identification/validation of circulating prognostic/predictive biomarkers in liquid biopsies (i.e metabolites, EVs, Immune cell subpopulations).