## 3 Metabolomics Applied to Marine Organisms in Cancer Studies  
Cancer is one of the deadliest human diseases, able to alter the metabolism of a cell [66]. It is well known that cancer metabolism is different from that of normal tissue, and an important hypothesis published in the 1950s by [PERSON] suggested that cancer cells use anaerobic metabolism as a source of energy [67]. In fact, the best-studied aspect of cancer metabolism is the central carbon metabolism and the relationships between glycolysis, the tricarboxylic acid (TCA) cycle and the oxidative phosphorylation [68]. One assumption is that cancer mainly converts pyruvate to lactate, rather than fuelling the TCA cycle, even in aerobic conditions [69,70]. The exploration of the cancer metabolome is the best way to understand the phenotypic changes associated to biological functions. Thanks to the metabolomics approach, it is possible to identify a range of metabolites involved in the process of carcinogenesis [71]. Moreover, a metabolomics approach is used for the discovery of biomarkers, and consequently, to improve the diagnosis and prognosis of many cancers, such as colorectal, breast, gastric, pancreatic and liver cancer [72]. In metabolomics, there are several approaches: fingerprinting, footprinting, profiling, flux analysis and target analysis. The first approach includes the screening of all metabolites within a biological system. Footprinting (mainly related to in vitro cell system) investigates metabolites from the environment around the system under analysis and shows information about metabolic exchange. Profiling is used to identify chemical compounds, for example lipids, also using standards for analyses. The fourth approach, called \"flux analysis\", is the detection of one compound, usually isotope-labelled carbon, through a specific pathway or set of pathways, to determine the destiny of the compound. Target analysis provides a comparison of one or a few target metabolites, whose concentrations can change depending on the environmental conditions [72,73]. According to an analysis of literature, in the last years, the marine environment has shown to be the most promising source of bioactive compounds against cancer. In particular, sponges and algae are likely to be the marine organisms from which the largest number of natural compounds with antiproliferative activity could be isolated. During the past 50 years, sponges are considered a gold mine for the discovery of bioactive natural products [74,75]. In fact, the first marine-derived anticancer compound, the cytarabine or Ara-C, which was approved in 1969 and is still used to treat acute myelocytic leukemia and non-Hodgkin's lymphoma, was isolated from the Caribbean sponge _Tethya crypta_[76]. In 2010 another anticancer agent, Eribulin, was isolated from the sponge _Halichondriaokadai_[77], developed from the polyether metabolite halichondrin B and commercialized as Halaven [78]. Algae, especially microalgae, have the same importance as a source of natural products, being easily cultivated in large-scale closed ensuring a theoretically limitless supply of biomass. Bioactive compounds of algal origin can be sourced directly from primary metabolism (e.g., proteins, fatty acids, vitamins and pigments) or can be synthesized from secondary metabolism [79]. Potent sunscreens against ultraviolet (UV)-induced cell damage were isolated from Spirulina, Chlorella and Donaliella [80; 81; 82; 83], as well as antioxidant carotenoids (astaxanthin, lutein, zeaxanthin, canthaxanthin and b-carotene) from _Dunaliella salina_[84; 85; 86; 87; 88]. In the frame of evolutive processes, several marine organisms, such as macro- and microalgae, sponges and fishes, developed appropriate defence mechanisms. They are based on the use of a variety of natural weapons, i.e., molecules that allow them to survive in a hostile environment characterized by stressful conditions. This is due to variable salinity, pressure, temperature and light, as well as to the need to avoid microbial and/or viral attacks [19].