title: Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the "Supply Problem".
abstract: Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current review we describe the main strategies aimed to overcome the supply problem. These include: marine invertebrate aquaculture, invertebrate and symbiont cell culture, culture-independent strategies, total chemical synthesis, semi-synthesis, and a number of hybrid strategies. We provide examples illustrating the application of these strategies for the supply of marine invertebrate-derived anticancer agents. Finally, we encourage the scientific community to develop scalable methods to obtain selected metabolites, which in the authors' opinion should be pursued due to their most promising anticancer activities.
authors.affiliation: REQUIMTE/LAQV, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal. goncalomortagua@hotmail.com.
authors.forename: Nelson G M
authors.initials: NG
authors.lastname: Gomes
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA. r_d127@txstate.edu.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Dasari
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA. schandra@txstate.edu.
authors.forename: Sunena
authors.initials: S
authors.lastname: Chandra
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Campus de la Plaine, CP205/1, Boulevard du Triomphe, 1050 Brussels, Belgium. rkiss@ulb.ac.be.
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA. a_k76@txstate.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kornienko
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D059001:Aquatic Organisms / Q000378:metabolism*; D001688:Biological Products / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D007448:Invertebrates / Q000378:metabolism*; D008386:Marine Biology / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products
keywords: discodermolide; eribulin; frondoside A; monanchocidin A; mycalamide A; phenylmethylene hydantoin; spongistatin 1; stelletin A; trabectedin