{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:33:45Z","timestamp":1790775225330,"version":"4.1.0"},"reference-count":224,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T00:00:00Z","timestamp":1507852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Despite the huge investment into research and the significant effort and advances made in the search for new anticancer drugs in recent decades, cancer cure and treatment continue to be a formidable challenge. Many sources, including plants, animals, and minerals, have been explored in the oncological field because of the possibility of identifying novel molecular therapeutics. Marine sponges are a prolific source of secondary metabolites, a number of which showed intriguing tumor chemopreventive and chemotherapeutic properties. Recently, Food and Drug Administration-approved drugs derived from marine sponges have been shown to reduce metastatic breast cancer, malignant lymphoma, and Hodgkin\u2019s disease. The chemopreventive and potential anticancer activity of marine sponge-derived compounds could be explained by multiple cellular and molecular mechanisms, including DNA protection, cell-cycle modulation, apoptosis, and anti-inflammatory activities as well as their ability to chemosensitize cancer cells to traditional antiblastic chemotherapy. The present article aims to depict the multiple mechanisms involved in the chemopreventive and therapeutic effects of marine sponges and critically explore the limitations and challenges associated with the development of marine sponge-based anticancer strategy.<\/jats:p>","DOI":"10.3390\/md15100310","type":"journal-article","created":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T11:34:09Z","timestamp":1507894449000},"page":"310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":149,"title":["Marine Sponge Natural Products with Anticancer Potential: An Updated Review"],"prefix":"10.3390","volume":"15","author":[{"given":"Cinzia","family":"Calcabrini","sequence":"first","affiliation":[{"name":"Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d\u2019Augusto 237, 47921 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7699-3414","authenticated-orcid":false,"given":"Elena","family":"Catanzaro","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d\u2019Augusto 237, 47921 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9159-960X","authenticated-orcid":false,"given":"Anupam","family":"Bishayee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4743-1126","authenticated-orcid":false,"given":"Eleonora","family":"Turrini","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d\u2019Augusto 237, 47921 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5539-3225","authenticated-orcid":false,"given":"Carmela","family":"Fimognari","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d\u2019Augusto 237, 47921 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1021\/np030096l","article-title":"Natural products as sources of new drugs over the period 1981\u20132002","volume":"66","author":"Newman","year":"2003","journal-title":"J. Nat. Prod."},{"key":"ref_2","unstructured":"(2017, July 06). World Health Organization. Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/fs297\/en\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1200\/JCO.2008.20.6235","article-title":"Perspectives for cancer prevention with natural compounds","volume":"27","author":"Amin","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.3390\/md8102619","article-title":"Antiviral lead compounds from marine sponges","volume":"8","author":"Sagar","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1039\/C4NP00144C","article-title":"Marine natural products","volume":"32","author":"Blunt","year":"2015","journal-title":"Nat. Prod. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4539","DOI":"10.3390\/md12084539","article-title":"Marine sponge derived natural products between 2001 and 2010: Trends and opportunities for discovery of bioactives","volume":"12","author":"Mehbub","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S1471-4892(01)00063-7","article-title":"Natural products in anticancer therapy","volume":"1","author":"Lopes","year":"2001","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.3390\/md9091580","article-title":"Recently confirmed apoptosis-inducing lead compounds isolated from marine sponge of potential relevance in cancer treatment","volume":"9","author":"Essack","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e975093","DOI":"10.4161\/23723556.2014.975093","article-title":"Molecular crosstalk between apoptosis, necroptosis, and survival signaling","volume":"2","author":"Kaiser","year":"2015","journal-title":"Mol. Cell. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"a008698","DOI":"10.1101\/cshperspect.a008698","article-title":"Death receptor-ligand systems in cancer, cell death, and inflammation","volume":"5","author":"Walczak","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s11010-009-0267-2","article-title":"Nf-\u03baB and cancer: How intimate is this relationship","volume":"336","author":"Prasad","year":"2010","journal-title":"Mol. Cell. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.gde.2008.01.020","article-title":"Nf-\u03baB and cancer-identifying targets and mechanisms","volume":"18","author":"Naugler","year":"2008","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"469309","DOI":"10.1155\/2014\/469309","article-title":"Aaptamines from the marine sponge Aaptos sp. Display anticancer activities in human cancer cell lines and modulate ap-1-, Nf-\u03baB-, and p53-dependent transcriptional activity in mouse jb6 cl41 cells","volume":"2014","author":"Dyshlovoy","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s10637-014-0185-3","article-title":"The marine natural product microsclerodermin a is a novel inhibitor of the nuclear factor kappa B and induces apoptosis in pancreatic cancer cells","volume":"33","author":"Guzman","year":"2015","journal-title":"Investig. New Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"24027","DOI":"10.18632\/oncotarget.8210","article-title":"Discovery and characterization of isofistularin-3, a marine brominated alkaloid, as a new DNA demethylating agent inducing cell cycle arrest and sensitization to trail in cancer cells","volume":"7","author":"Florean","year":"2016","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.3390\/md11041140","article-title":"Spongiatriol inhibits nuclear factor kappa B activation and induces apoptosis in pancreatic cancer cells","volume":"11","author":"Guzman","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_18","first-page":"653","article-title":"Laulimalide and isolaulimalide, new paclitaxel-like microtubule-stabilizing agents","volume":"59","author":"Mooberry","year":"1999","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"De Stefano, D., Tommonaro, G., Malik, S.A., Iodice, C., De Rosa, S., Maiuri, M.C., and Carnuccio, R. (2012). Cacospongionolide and scalaradial, two marine sesterterpenoids as potent apoptosis-inducing factors in human carcinoma cell lines. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033031"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1093\/jnci\/djn239","article-title":"Induction of apoptosis in human cancer cells by candidaspongiolide, a novel sponge polyketide","volume":"100","author":"Trisciuoglio","year":"2008","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11418-009-0363-3","article-title":"Polyacetylene diols with antiproliferative and driving Th1 polarization effects from the marine sponge Callyspongia sp.","volume":"64","author":"Umeyama","year":"2010","journal-title":"J. Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"83071","DOI":"10.18632\/oncotarget.13068","article-title":"Marine guanidine alkaloids crambescidins inhibit tumor growth and activate intrinsic apoptotic signaling inducing tumor regression in a colorectal carcinoma zebrafish xenograft model","volume":"7","author":"Roel","year":"2016","journal-title":"Oncotarget"},{"key":"ref_23","first-page":"480","article-title":"Smenospongine, a sesquiterpene aminoquinone from a marine sponge, induces g1 arrest or apoptosis in different leukemia cells","volume":"6","author":"Kong","year":"2008","journal-title":"Mar. Drugs"},{"key":"ref_24","first-page":"517","article-title":"Induction of apoptosis by pectenotoxin-2 is mediated with the induction of DR4\/DR5, EGR-1 and NAG-1, activation of caspases and modulation of the Bcl-2 family in p53-deficient Hep3B hepatocellular carcinoma cells","volume":"19","author":"Shin","year":"2008","journal-title":"Oncol. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.canlet.2008.05.034","article-title":"Pectenotoxin-2 abolishes constitutively activated Nf-\u03baB, leading to suppression of Nf-\u03baB related gene products and potentiation of apoptosis","volume":"271","author":"Kim","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.bcp.2008.05.006","article-title":"Induction of G2\/M arrest, endoreduplication, and apoptosis by actin depolymerization agent pextenotoxin-2 in human leukemia cells, involving activation of erk and jnk","volume":"76","author":"Moon","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1007\/s10637-010-9521-4","article-title":"Salarin c, a member of the salarin superfamily of marine compounds, is a potent inducer of apoptosis","volume":"30","author":"Bishara","year":"2012","journal-title":"Investig. New Drugs"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1080\/15384101.2015.1078029","article-title":"Salarin C inhibits the maintenance of chronic myeloid leukemia progenitor cells","volume":"14","author":"Tanturli","year":"2015","journal-title":"Cell Cycle"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4424","DOI":"10.4161\/cc.22768","article-title":"Lasonolide a, a potent and reversible inducer of chromosome condensation","volume":"11","author":"Zhang","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3390\/md8010080","article-title":"Geoditin a induces oxidative stress and apoptosis on human colon HT29 cells","volume":"8","author":"Cheung","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.canlet.2004.12.034","article-title":"Apoptotic activity of isomalabaricane triterpenes on human promyelocytic leukemia hl60 cells","volume":"230","author":"Liu","year":"2005","journal-title":"Cancer Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1021\/np058122y","article-title":"Stellettin a induces oxidative stress and apoptosis in hl-60 human leukemia and lncap prostate cancer cell lines","volume":"69","author":"Liu","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.fct.2014.06.001","article-title":"Ilimaquinone induces death receptor expression and sensitizes human colon cancer cells to trail-induced apoptosis through activation of ros-erk\/p38 mapk-chop signaling pathways","volume":"71","author":"Do","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"543","DOI":"10.3390\/md13010543","article-title":"Activation of p53 with ilimaquinone and ethylsmenoquinone, marine sponge metabolites, induces apoptosis and autophagy in colon cancer cells","volume":"13","author":"Lee","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ejphar.2006.10.061","article-title":"Ilimaquinone, a marine sponge metabolite, displays anticancer activity via gadd153-mediated pathway","volume":"556","author":"Lu","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1158\/1535-7163.MCT-08-1179","article-title":"Bh3-only proteins mcl-1 and bim as well as endonuclease g are targeted in spongistatin 1-induced apoptosis in breast cancer cells","volume":"8","author":"Schneiders","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1038\/leu.2008.146","article-title":"Spongistatin 1: A new chemosensitizing marine compound that degrades xiap","volume":"22","author":"Schyschka","year":"2008","journal-title":"Leukemia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1002\/ijc.25241","article-title":"The marine compound spongistatin 1 targets pancreatic tumor progression and metastasis","volume":"127","author":"Rothmeier","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.bcp.2009.09.027","article-title":"Heteronemin, a spongean sesterterpene, inhibits tnf alpha-induced NF-\u03baB activation through proteasome inhibition and induces apoptotic cell death","volume":"79","author":"Schumacher","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1002\/pros.23230","article-title":"Heteronemin is a novel c-Met\/STAT3 inhibitor against advanced prostate cancer cells","volume":"76","author":"Wu","year":"2016","journal-title":"Prostate"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.2147\/IJN.S99911","article-title":"Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation","volume":"11","author":"Huang","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_42","first-page":"738241","article-title":"Heteronemin, a spongean sesterterpene, induces cell apoptosis and autophagy in human renal carcinoma cells","volume":"2015","author":"Wu","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/00001813-200603000-00005","article-title":"Bastadin 6, a spongean brominated tyrosine derivative, inhibits tumor angiogenesis by inducing selective apoptosis to endothelial cells","volume":"17","author":"Aoki","year":"2006","journal-title":"Anticancer Drugs"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.toxlet.2010.09.017","article-title":"Irciniastatin a induces jnk activation that is involved in caspase-8-dependent apoptosis via the mitochondrial pathway","volume":"199","author":"Chinen","year":"2010","journal-title":"Toxicol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.canlet.2007.11.039","article-title":"Induction of apoptosis accompanying with g(1) phase arrest and microtubule disassembly in human hepatoma cells by jaspolide b, a new isomalabaricane-type triterpene","volume":"262","author":"Wei","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"28906","DOI":"10.18632\/oncotarget.15957","article-title":"Stellettin b induces apoptosis in human chronic myeloid leukemia cells via targeting pi3k and stat5","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"27071","DOI":"10.1038\/srep27071","article-title":"Stellettin b induces g1 arrest, apoptosis and autophagy in human non-small cell lung cancer A549 cells via blocking PI3K\/Akt\/mTOR pathway","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4200","DOI":"10.3390\/md12074200","article-title":"In vitro antitumor activity of stellettin b, a triterpene from marine sponge jaspis stellifera, on human glioblastoma cancer sf295 cells","volume":"12","author":"Tang","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.bcp.2009.05.002","article-title":"The natural marine anhydrophytosphingosine, jaspine b, induces apoptosis in melanoma cells by interfering with ceramide metabolism","volume":"78","author":"Salma","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1002\/ptr.4673","article-title":"Pachastrissamine from Pachastrissa sp. Inhibits melanoma cell growth by dual inhibition of Cdk2 and erk-mediated foxo3 downregulation","volume":"26","author":"Yoo","year":"2012","journal-title":"Phytother. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4584","DOI":"10.1016\/j.bmcl.2009.06.097","article-title":"C29 sterols with a cyclopropane ring at C-25 and 26 from the vietnamese marine sponge ianthella sp. In addition, their anticancer properties","volume":"19","author":"Nguyen","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1002\/ijc.30253","article-title":"Leiodermatolide, a novel marine natural product, has potent cytotoxic and antimitotic activity against cancer cells, appears to affect microtubule dynamics, and exhibits antitumor activity","volume":"139","author":"Guzman","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/CAD.0b013e32832ae55f","article-title":"The marine alkaloid naamidine a promotes caspase-dependent apoptosis in tumor cells","volume":"20","author":"LaBarbera","year":"2009","journal-title":"Anticancer Drugs"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Dyshlovoy, S.A., Tabakmakher, K.M., Hauschild, J., Shchekaleva, R.K., Otte, K., Guzii, A.G., Makarieva, T.N., Kudryashova, E.K., Fedorov, S.N., and Shubina, L.K. (2016). Guanidine alkaloids from the marine sponge monanchora pulchra show cytotoxic properties and prevent egf-induced neoplastic transformation in vitro. Mar. Drugs, 14.","DOI":"10.3390\/md14070133"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1023\/A:1011340827558","article-title":"Induction of apoptosis by the marine sponge (mycale) metabolites, mycalamide a and pateamine","volume":"6","author":"Hood","year":"2001","journal-title":"Apoptosis"},{"key":"ref_56","first-page":"2091","article-title":"Latrunculin a has a strong anticancer effect in a peritoneal dissemination model of human gastric cancer in mice","volume":"29","author":"Konishi","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3390\/md502006","article-title":"Anticancer activity evaluation of kuanoniamines a and c isolated from the marine sponge oceanapia sagittaria, collected from the gulf of thailand","volume":"5","author":"Kijjoa","year":"2007","journal-title":"Mar. Drugs"},{"key":"ref_58","first-page":"1091","article-title":"Induction of apoptosis by dideoxypetrosynol a, a polyacetylene from the sponge petrosia sp., in human skin melanoma cells","volume":"14","author":"Choi","year":"2004","journal-title":"Int. J. Mol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ygyno.2007.08.098","article-title":"A natural histone deacetylase inhibitor, psammaplin a, induces cell cycle arrest and apoptosis in human endometrial cancer cells","volume":"108","author":"Ahn","year":"2008","journal-title":"Gynecol. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ygyno.2008.10.017","article-title":"Induction of apoptosis in endometrial cancer cells by psammaplysene a involves foxo1","volume":"112","author":"Berry","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.3390\/md11093168","article-title":"Towards the small and the beautiful: A small dibromotyrosine derivative from Pseudoceratina sp. sponge exhibits potent apoptotic effect through targeting IKK\/NF\u03baB signaling pathway","volume":"11","author":"Su","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.cellbi.2007.08.009","article-title":"Rhabdastrellic acid-a inhibited pi3k\/akt pathway and induced apoptosis in human leukemia hl-60 cells","volume":"32","author":"Guo","year":"2008","journal-title":"Cell. Biol. Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1248\/bpb.32.955","article-title":"Differential induction of apoptosis of leukemic cells by rhizochalin, two headed sphingolipids from sponge and its derivatives","volume":"32","author":"Jin","year":"2009","journal-title":"Biol. Pharm. Bull."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1248\/bpb.34.1553","article-title":"Aglycon of rhizochalin from the rhizochalina incrustata induces apoptosis via activation of amp-activated protein kinase in ht-29 colon cancer cells","volume":"34","author":"Khanal","year":"2011","journal-title":"Biol. Pharm. Bull."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s11745-009-3322-6","article-title":"Marine two-headed sphingolipid-like compound rhizochalin inhibits egf-induced transformation of jb6 p+ cl41 cells","volume":"44","author":"Fedorov","year":"2009","journal-title":"Lipids"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"69703","DOI":"10.18632\/oncotarget.11941","article-title":"Marine compound rhizochalinin shows high in vitro and in vivo efficacy in castration resistant prostate cancer","volume":"7","author":"Dyshlovoy","year":"2016","journal-title":"Oncotarget"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/mc.20084","article-title":"Ircinin-1 induces cell cycle arrest and apoptosis in sk-mel-2 human melanoma cells","volume":"44","author":"Choi","year":"2005","journal-title":"Mol. Carcinog."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1515\/znc-2015-0160","article-title":"Antiproliferative effects of triterpenoidal derivatives, obtained from the marine sponge Siphonochalina sp., on human hepatic and colorectal cancer cells","volume":"71","author":"Alahdal","year":"2016","journal-title":"Z. Naturforsch. C"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.4103\/0973-1296.203970","article-title":"Cytotoxic metabolites from callyspongia siphonella display antiproliferative activity by inducing apoptosis in hct-116 cells","volume":"13","author":"Sobahi","year":"2017","journal-title":"Pharmacogn. Mag."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4451","DOI":"10.3390\/md11114451","article-title":"Smenamides a and b, chlorinated peptide\/polyketide hybrids containing a dolapyrrolidinone unit from the caribbean sponge Smenospongia aurea. Evaluation of their role as leads in antitumor drug research","volume":"11","author":"Teta","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1159\/000100809","article-title":"Induction of apoptosis by (z)-stellettic acid c, an acetylenic acid from the sponge Stelletta sp., is associated with inhibition of telomerase activity in human leukemic u937 cells","volume":"53","author":"Park","year":"2007","journal-title":"Chemotherapy"},{"key":"ref_72","first-page":"193","article-title":"Anticancer and antimetastatic activities of renieramycin m, a marine tetrahydroisoquinoline alkaloid, in human non-small cell lung cancer cells","volume":"31","author":"Halim","year":"2011","journal-title":"Anticancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1475-2867-12-14","article-title":"Molecular network profiling of u373mg human glioblastoma cells following induction of apoptosis by novel marine-derived anti-cancer 1,2,3,4-tetrahydroisoquinoline alkaloids","volume":"12","author":"Tabunoki","year":"2012","journal-title":"Cancer Cell. Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1007\/s12325-016-0344-3","article-title":"Trabectedin for soft tissue sarcoma: Current status and future perspectives","volume":"33","author":"Gordon","year":"2016","journal-title":"Adv. Ther."},{"key":"ref_75","unstructured":"FDA (2017, September 18). Fda Approves New Therapy for Certain Types of Advanced Soft Tissue Sarcoma, Available online: https:\/\/www.fda.gov\/newsevents\/newsroom\/pressannouncements\/ucm468832.htm."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4548","DOI":"10.1016\/j.bmc.2009.05.009","article-title":"Chemistry of renieramycins. Part 8: Synthesis and cytotoxicity evaluation of renieramycin m-jorunnamycin a analogues","volume":"17","author":"Charupant","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.1016\/j.tet.2004.02.071","article-title":"Chemistry of renieramycins. Part 6: Transformation of renieramycin m into jorumycin and renieramycin j including oxidative degradation products, mimosamycin, renierone, and renierol acetate","volume":"60","author":"Saito","year":"2004","journal-title":"Tetrahedron"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1083\/jcb.124.4.619","article-title":"Disruption of epithelial cell-matrix interactions induces apoptosis","volume":"124","author":"Frisch","year":"1994","journal-title":"J. Cell. Biol."},{"key":"ref_79","first-page":"1665","article-title":"Renieramycin m sensitizes anoikis-resistant h460 lung cancer cells to anoikis","volume":"36","author":"Sirimangkalakitti","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"615","DOI":"10.21873\/anticanres.11355","article-title":"Renieramycin m attenuates cancer stem cell-like phenotypes in h460 lung cancer cells","volume":"37","author":"Sirimangkalakitti","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/nrc1209","article-title":"Ap-1: A double-edged sword in tumorigenesis","volume":"3","author":"Eferl","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/j.fct.2007.09.082","article-title":"Anticarcinogenesis by dietary phytochemicals: Cytoprotection by nrf2 in normal cells and cytotoxicity by modulation of transcription factors NF-\u03baB and ap-1 in abnormal cancer cells","volume":"46","author":"Gopalakrishnan","year":"2008","journal-title":"Food. Chem. Toxicol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S1097-2765(00)80054-4","article-title":"DNA damaging agents induce expression of fas ligand and subsequent apoptosis in t lymphocytes via the activation of NF-\u03baB b and ap-1","volume":"1","author":"Kasibhatla","year":"1998","journal-title":"Mol. Cell."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.2174\/138945011796150280","article-title":"Foxo1: A potential target for human diseases","volume":"12","author":"Lu","year":"2011","journal-title":"Curr. Drug Targets"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7421","DOI":"10.1073\/pnas.96.13.7421","article-title":"Protein kinase b\/akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor fkhr1","volume":"96","author":"Biggs","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0092-8674(00)80595-4","article-title":"Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor","volume":"96","author":"Brunet","year":"1999","journal-title":"Cell"},{"key":"ref_87","first-page":"3935","article-title":"Mutations in pten are frequent in endometrial carcinoma but rare in other common gynecological malignancies","volume":"57","author":"Tashiro","year":"1997","journal-title":"Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/sj.onc.1210626","article-title":"Mechanism and functional consequences of loss of foxo1 expression in endometrioid endometrial cancer cells","volume":"27","author":"Goto","year":"2008","journal-title":"Oncogene"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1210\/en.2007-0756","article-title":"The regulation and function of the forkhead transcription factor, forkhead box O1, is dependent on the progesterone receptor in endometrial carcinoma","volume":"149","author":"Ward","year":"2008","journal-title":"Endocrinology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1158\/0008-5472.CAN-11-4141","article-title":"Oncogenic pi3k mutations lead to Nf-\u03baB-dependent cytokine expression following growth factor deprivation","volume":"72","author":"Hutti","year":"2012","journal-title":"Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.canlet.2012.02.008","article-title":"The novel Nf-\u03baB inhibitor dhmeq synergizes with celecoxib to exert antitumor effects on human liver cancer cells by a ros-dependent mechanism","volume":"322","author":"Lampiasi","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1479-5876-10-53","article-title":"Nf-\u03baB as potential target in the treatment of melanoma","volume":"10","author":"Madonna","year":"2012","journal-title":"J. Transl. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1007\/s10495-009-0341-y","article-title":"Cellular responses to endoplasmic reticulum stress and apoptosis","volume":"14","author":"Rasheva","year":"2009","journal-title":"Apoptosis"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1196\/annals.1299.032","article-title":"Caspase-12 and er-stress-mediated apoptosis: The story so far","volume":"1010","author":"Szegezdi","year":"2003","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/47513","article-title":"Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta","volume":"403","author":"Nakagawa","year":"2000","journal-title":"Nature"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1093\/hmg\/ddi396","article-title":"Endoplasmic reticulum stress and mitochondrial cell death pathways mediate A53T mutant alpha-synuclein-induced toxicity","volume":"14","author":"Smith","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_97","first-page":"156","article-title":"Cytotoxic effects of some animal and vegetable extracts and some chemicals on liver and colon carcinoma and myosarcoma","volume":"25","author":"Bayazit","year":"2004","journal-title":"Saudi Med. J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"204975","DOI":"10.1155\/2015\/204975","article-title":"Anti-inflammatory effects of a methanol extract from the marine sponge Geodia cydonium on the human breast cancer MCF-7 cell line","volume":"2015","author":"Costantini","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_99","first-page":"291","article-title":"Inhibition of cyclooxygenase-2 and telomerase activities in human leukemia cells by dideoxypetrosynol a, a polyacetylene from the marine sponge Petrosia sp.","volume":"30","author":"Park","year":"2007","journal-title":"Int. J. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1159\/000071373","article-title":"Therapeutic potential of selective cyclooxygenase-2 inhibitors in the management of tumor angiogenesis","volume":"37","author":"Gately","year":"2003","journal-title":"Prog. Exp. Tumor. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"33157","DOI":"10.1074\/jbc.271.52.33157","article-title":"Prostaglandin endoperoxide h synthases (cyclooxygenases)-1 and -2","volume":"271","author":"Smith","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/jcp.10068","article-title":"Many actions of cyclooxygenase-2 in cellular dynamics and in cancer","volume":"190","author":"Cao","year":"2002","journal-title":"J. Cell. Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"6735","DOI":"10.1158\/1078-0432.CCR-07-4843","article-title":"The interleukin-8 pathway in cancer","volume":"14","author":"Waugh","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/CAD.0000000000000443","article-title":"Inhibition of il-8 secretion on bxpc-3 and mia paca-2 cells and induction of cytotoxicity in pancreatic cancer cells with marine natural products","volume":"28","author":"Guzman","year":"2017","journal-title":"Anticancer Drugs"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1038\/sj.onc.1208618","article-title":"Cyclins and cdks in development and cancer: A perspective","volume":"24","author":"Deshpande","year":"2005","journal-title":"Oncogene"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1021\/pr300170p","article-title":"Proteomic profiling of germ cell cancer cells treated with aaptamine, a marine alkaloid with antiproliferative activity","volume":"11","author":"Dyshlovoy","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"291","DOI":"10.2174\/1871520614666141114201027","article-title":"The cytotoxic and mechanistic effects of aaptamine on hepatocellular carcinoma","volume":"15","author":"Li","year":"2015","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.bbrc.2006.01.119","article-title":"Aaptamine, a spongean alkaloid, activates p21 promoter in a p53-independent manner","volume":"342","author":"Aoki","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"7352","DOI":"10.3390\/ijms12117352","article-title":"Antiproliferative effect of aaptamine on human chronic myeloid leukemia k562 cells","volume":"12","author":"Jin","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1021\/np900183v","article-title":"Isolation, synthesis, and biological activity of aphrocallistin, an adenine-substituted bromotyramine metabolite from the hexactinellida sponge Aphrocallistes beatrix","volume":"72","author":"Wright","year":"2009","journal-title":"J. Nat. Prod."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/1097-0215(20001201)88:5<810::AID-IJC20>3.0.CO;2-P","article-title":"Mechanism of action of aragusterol a (yta0040), a potent anti-tumor marine steroid targeting the g(1) phase of the cell cycle","volume":"88","author":"Fukuoka","year":"2000","journal-title":"Int. J. Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/CAD.0b013e32831fa39e","article-title":"Selective cytotoxic activity of the marine-derived batzelline compounds against pancreatic cancer cell lines","volume":"20","author":"Guzman","year":"2009","journal-title":"Anticancer Drugs"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3390\/toxins3010105","article-title":"The discodermia calyx toxin calyculin a enhances cyclin d1 phosphorylation and degradation, and arrests cell cycle progression in human breast cancer cells","volume":"3","author":"Edelson","year":"2011","journal-title":"Toxins"},{"key":"ref_114","first-page":"2325","article-title":"Erythroid differentiation in k562 chronic myelogenous cells induced by crambescidin 800, a pentacyclic guanidine alkaloid","volume":"24","author":"Aoki","year":"2004","journal-title":"Anticancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0006-2952(03)00192-8","article-title":"Tubulin polymerizing activity of dictyostatin-1, a polyketide of marine sponge origin","volume":"66","author":"Isbrucker","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_116","first-page":"171","article-title":"Suppression of u937 human monocytic leukemia cell growth by dideoxypetrosynol a, a polyacetylene from the sponge Petrosia sp., via induction of cdk inhibitor p16 and down-regulation of prb phosphorylation","volume":"16","author":"Park","year":"2006","journal-title":"Oncol. Rep."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1021\/bi9515127","article-title":"Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol","volume":"35","author":"Kowalski","year":"1996","journal-title":"Biochemistry"},{"key":"ref_118","first-page":"1303","article-title":"Suppression of microtubule dynamics by discodermolide by a novel mechanism is associated with mitotic arrest and inhibition of tumor cell proliferation","volume":"2","author":"Honore","year":"2003","journal-title":"Mol. Cancer Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1016\/j.peptides.2006.04.021","article-title":"Cytoskeleton alterations induced by geodia corticostylifera depsipeptides in breast cancer cells","volume":"27","author":"Rangel","year":"2006","journal-title":"Peptides"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.tiv.2012.11.001","article-title":"Anti-proliferative effect of (19Z)-halichondramide, a novel marine macrolide isolated from the sponge Chondrosia corticata, is associated with G2\/M cell cycle arrest and suppression of mtor signaling in human lung cancer cells","volume":"27","author":"Bae","year":"2013","journal-title":"Toxicol In Vitro"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s002800050564","article-title":"Cytotoxic peptides hemiasterlin, hemiasterlin a and hemiasterlin b induce mitotic arrest and abnormal spindle formation","volume":"39","author":"Anderson","year":"1997","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1002\/anie.201007719","article-title":"Leiodermatolide, a potent antimitotic macrolide from the marine sponge leiodermatium sp.","volume":"50","author":"Paterson","year":"2011","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"15719","DOI":"10.1021\/ja508846g","article-title":"Synthesis, molecular editing, and biological assessment of the potent cytotoxin leiodermatolide","volume":"136","author":"Mailhol","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s002800050019","article-title":"Different microtubule network alterations induced by pachymatismin, a new marine glycoprotein, on two prostatic cell lines","volume":"45","author":"Sangrajrang","year":"2000","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_125","first-page":"2805","article-title":"Effects in vitro of pachymatismin, a glycoprotein from the marine sponge Pachymatisma johnstonii, on a non-small-cell bronchopulmonary carcinoma line (nsclc-n6)","volume":"16","author":"Zidane","year":"1996","journal-title":"Anticancer Res."},{"key":"ref_126","first-page":"185","article-title":"In vivo effect of pachymatismin, a new marine glycoprotein, on a human non-small-cell lung carcinoma","volume":"11","author":"Zidane","year":"1997","journal-title":"In Vivo"},{"key":"ref_127","first-page":"3356","article-title":"Peloruside a, a novel antimitotic agent with paclitaxel-like microtubule- stabilizing activity","volume":"62","author":"Hood","year":"2002","journal-title":"Cancer Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s10637-010-9398-2","article-title":"Peloruside a inhibits microtubule dynamics in a breast cancer cell line MCF7","volume":"29","author":"Chan","year":"2011","journal-title":"Investig. New Drugs"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1006\/bbrc.2001.4588","article-title":"Differentiation in chronic myelogenous leukemia cell k562 by spongean sesterterpene","volume":"282","author":"Aoki","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_130","first-page":"957","article-title":"Mechanism of cell cycle arrest by (8e, 13z, 20z)-strobilinin\/(7e, 13z, 20z)-felixinin from a marine sponge Psammocinia sp.","volume":"14","author":"Jiang","year":"2005","journal-title":"Oncol. Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1021\/cb400461j","article-title":"New interfacial microtubule inhibitors of marine origin, pm050489\/pm060184, with potent antitumor activity and a distinct mechanism","volume":"8","author":"Pera","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.bcp.2014.01.026","article-title":"Pm060184, a new tubulin binding agent with potent antitumor activity including p-glycoprotein over-expressing tumors","volume":"88","author":"Pera","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"S334","DOI":"10.4103\/0973-1296.133292","article-title":"Cytotoxic neviotane triterpene-type from the red sea sponge Siphonochalina siphonella","volume":"10","author":"Angawi","year":"2014","journal-title":"Pharmacogn. Mag."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1097\/00001813-200404000-00009","article-title":"Smenospongine, a spongean sesquiterpene aminoquinone, induces erythroid differentiation in k562 cells","volume":"15","author":"Aoki","year":"2004","journal-title":"Anticancer Drugs"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"D1209","DOI":"10.2741\/A357","article-title":"Protein phosphatase type 1, the product of the retinoblastoma susceptibility gene, and cell cycle control","volume":"3","author":"Rubin","year":"1998","journal-title":"Front. Biosci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/289068a0","article-title":"Expression of cell-surface HLA-DR, HLA-ABC and glycophorin during erythroid differentiation","volume":"289","author":"Robinson","year":"1981","journal-title":"Nature"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1182\/blood.V84.9.2912.2912","article-title":"Identification of crkl as the constitutively phosphorylated 39-kd tyrosine phosphoprotein in chronic myelogenous leukemia cells","volume":"84","author":"Nichols","year":"1994","journal-title":"Blood"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"690916","DOI":"10.1155\/2015\/690916","article-title":"Stabilizing versus destabilizing the microtubules: A double-edge sword for an effective cancer treatment option?","volume":"2015","author":"Fanale","year":"2015","journal-title":"Anal. Cell. Pathol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"13684","DOI":"10.1073\/pnas.1414572111","article-title":"A previously undescribed tubulin binder","volume":"111","author":"Field","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.3390\/md8041059","article-title":"Microtubule-stabilizing drugs from marine sponges: Focus on peloruside a and zampanolide","volume":"8","author":"Miller","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.lfs.2016.02.034","article-title":"Dictyoceratidan poisons: Defined mark on microtubule-tubulin dynamics","volume":"148","author":"Gnanambal","year":"2016","journal-title":"Life Sci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1124\/mol.52.4.613","article-title":"The microtubule-stabilizing agent discodermolide competitively inhibits the binding of paclitaxel (taxol) to tubulin polymers, enhances tubulin nucleation reactions more potently than paclitaxel, and inhibits the growth of paclitaxel-resistant cells","volume":"52","author":"Kowalski","year":"1997","journal-title":"Mol. Pharmacol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"5063","DOI":"10.1158\/0008-5472.CAN-04-0771","article-title":"Peloruside a does not bind to the taxoid site on beta-tubulin and retains its activity in multidrug-resistant cell lines","volume":"64","author":"Gaitanos","year":"2004","journal-title":"Cancer Res."},{"key":"ref_144","unstructured":"Northcote, P.T., Miller, J.H., Hood, K.A., and West, L.M. (2004). Bioactive Compound. (6,790,862 B), U.S. Patent."},{"key":"ref_145","unstructured":"Rowe, M.R. (2015). Resistance to Microtubule-Stabilising Agents Following Point Mutation of Human \u03b2i-Tubulin. [Master\u2019s Thesis, Victoria University of Wellington]."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1158\/1535-7163.MCT-15-0167","article-title":"Peloruside a inhibits growth of human lung and breast tumor xenografts in an athymic nu\/nu mouse model","volume":"14","author":"Meyer","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1039\/C5NP00146C","article-title":"Peloruside a: A lead non-taxoid-site microtubule-stabilizing agent with potential activity against cancer, neurodegeneration, and autoimmune disease","volume":"33","author":"Kanakkanthara","year":"2016","journal-title":"Nat. Prod. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"79","DOI":"10.2174\/1568009613666131113101151","article-title":"Resistance to peloruside a and laulimalide: Functional significance of acquired betai-tubulin mutations at sites important for drug-tubulin binding","volume":"14","author":"Kanakkanthara","year":"2014","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1007\/s11095-012-0773-x","article-title":"Acquired resistance to peloruside a and laulimalide is associated with downregulation of vimentin in human ovarian carcinoma cells","volume":"29","author":"Kanakkanthara","year":"2012","journal-title":"Pharm. Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"13817","DOI":"10.1073\/pnas.1408124111","article-title":"A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs","volume":"111","author":"Prota","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrc706","article-title":"Multidrug resistance in cancer: Role of atp-dependent transporters","volume":"2","author":"Gottesman","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrc3599","article-title":"Cancer drug resistance: An evolving paradigm","volume":"13","author":"Holohan","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_153","first-page":"3352","article-title":"Rapid activation of mdr1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin","volume":"5","author":"Abolhoda","year":"1999","journal-title":"Clin. Cancer Res."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Gameiro, M., Silva, R., Rocha-Pereira, C., Carmo, H., Carvalho, F., Bastos, M.L., and Remiao, F. (2017). Cellular models and in vitro assays for the screening of modulators of p-gp, mrp1 and bcrp. Molecules, 22.","DOI":"10.3390\/molecules22040600"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.drup.2016.05.001","article-title":"Overcoming abc transporter-mediated multidrug resistance: Molecular mechanisms and novel therapeutic drug strategies","volume":"27","author":"Li","year":"2016","journal-title":"Drug Resist. Updates"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.3892\/ol.2015.3777","article-title":"Increased activity of chk enhances the radioresistance of MCF-7 breast cancer stem cells","volume":"10","author":"Yang","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_157","first-page":"1978","article-title":"Taxol and discodermolide represent a synergistic drug combination in human carcinoma cell lines","volume":"6","author":"Martello","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.1158\/0008-5472.CAN-04-0693","article-title":"Synergistic suppression of microtubule dynamics by discodermolide and paclitaxel in non-small cell lung carcinoma cells","volume":"64","author":"Honore","year":"2004","journal-title":"Cancer Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1158\/1078-0432.CCR-05-0229","article-title":"Potentiation of taxol efficacy and by discodermolide in ovarian carcinoma xenograft-bearing mice","volume":"12","author":"Huang","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.3390\/md12031377","article-title":"Cytotoxic effects of fascaplysin against small cell lung cancer cell lines","volume":"12","author":"Hamilton","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"22282","DOI":"10.18632\/oncotarget.4162","article-title":"Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of patched and increase chemotherapy efficiency on melanoma cells","volume":"6","author":"Fiorini","year":"2015","journal-title":"Oncotarget"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1021\/mp060101p","article-title":"Peloruside a synergizes with other microtubule stabilizing agents in cultured cancer cell lines","volume":"4","author":"Wilmes","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.3390\/md12073818","article-title":"Lamellarin o, a pyrrole alkaloid from an australian marine sponge, Ianthella sp., reverses bcrp mediated drug resistance in cancer cells","volume":"12","author":"Huang","year":"2014","journal-title":"Mar Drugs"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1111\/j.1349-7006.2001.tb01177.x","article-title":"Reversing effect of agosterol a, a spongean sterol acetate, on multidrug resistance in human carcinoma cells","volume":"92","author":"Aoki","year":"2001","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/ijc.1290","article-title":"Reversal of drug resistance mediated by multidrug resistance protein (mrp) 1 by dual effects of agosterol a on mrp1 function","volume":"93","author":"Chen","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1016\/j.bcp.2010.08.001","article-title":"Marine sponge-derived sipholane triterpenoids reverse p-glycoprotein (abcb1)-mediated multidrug resistance in cancer cells","volume":"80","author":"Abraham","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1111\/j.1349-7006.2007.00554.x","article-title":"Sipholenol a, a marine-derived sipholane triterpene, potently reverses p-glycoprotein (abcb1)-mediated multidrug resistance in cancer cells","volume":"98","author":"Shi","year":"2007","journal-title":"Cancer Sci."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1177\/1758834010366430","article-title":"Targeting the hedgehog pathway in cancer","volume":"2","author":"Gupta","year":"2010","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1158\/1541-7786.MCR-11-0578","article-title":"The hedgehog receptor patched functions in multidrug transport and chemotherapy resistance","volume":"10","author":"Bidet","year":"2012","journal-title":"Mol. Cancer Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1021\/np1000818","article-title":"Terpenoids and a flavonoid glycoside from acacia pennata leaves as hedgehog\/gli-mediated transcriptional inhibitors","volume":"73","author":"Rifai","year":"2010","journal-title":"J. Nat. Prod."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"3471","DOI":"10.1016\/S0040-4039(03)00671-3","article-title":"Structures and cytotoxicities of fascaplysin and related alkaloids from two marine phyla\u2014Fascaplysinopsis sponges and didemnum tunicates","volume":"44","author":"Segraves","year":"2003","journal-title":"Tetrahedron Lett."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.4161\/cc.20135","article-title":"Manzamines: A potential for novel cures","volume":"11","author":"Radwan","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s10637-010-9422-6","article-title":"A novel activity from an old compound: Manzamine a reduces the metastatic potential of aspc-1 pancreatic cancer cells and sensitizes them to trail-induced apoptosis","volume":"29","author":"Guzman","year":"2011","journal-title":"Investig. New Drugs"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Manohar, S., and Leung, N. (2017). Cisplatin nephrotoxicity: A review of the literature. J. Nephrol.","DOI":"10.1007\/s40620-017-0392-z"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s00405-016-4117-z","article-title":"Platinum-induced ototoxicity: A review of prevailing ototoxicity criteria","volume":"274","author":"Waissbluth","year":"2017","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"46663","DOI":"10.18632\/oncotarget.16944","article-title":"Autophagy and mitophagy in the context of doxorubicin-induced cardiotoxicity","volume":"8","author":"Koleini","year":"2017","journal-title":"Oncotarget"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1177\/1078155215574294","article-title":"The role of screening and monitoring for bleomycin pulmonary toxicity","volume":"22","author":"Shippee","year":"2016","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1021\/np300794b","article-title":"Aaptamine derivatives from the indonesian sponge Aaptos suberitoides","volume":"76","author":"Pham","year":"2013","journal-title":"J. Nat. Prod."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1023\/B:JOEC.0000006475.10310.3a","article-title":"Wound activation of protoxins in marine sponge Aplysina aerophoba","volume":"23","author":"Ebel","year":"1997","journal-title":"J. Chem. Ecol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1097\/CAD.0000000000000119","article-title":"Spongean alkaloids protect rat kidney cells against cisplatin-induced cytotoxicity","volume":"25","author":"Funk","year":"2014","journal-title":"Anticancer Drugs"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Khalil, H.S., Tummala, H., Chakarov, S., Zhelev, N., and Lane, D.P. (2012). Targeting atm pathway for therapeutic intervention in cancer. Biodiscovery.","DOI":"10.7750\/BioDiscovery.2012.1.3"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"17914","DOI":"10.1074\/jbc.M100728200","article-title":"Inhibition of the g2 DNA damage checkpoint and of protein kinases chk1 and chk2 by the marine sponge alkaloid debromohymenialdisine","volume":"276","author":"Curman","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1111\/j.1476-5381.2009.00607.x","article-title":"Oxaliplatin responses in colorectal cancer cells are modulated by chk2 kinase inhibitors","volume":"159","author":"Pires","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_184","first-page":"1843","article-title":"The microtubule-affecting drug paclitaxel has antiangiogenic activity","volume":"2","author":"Belotti","year":"1996","journal-title":"Clin. Cancer Res."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"276","DOI":"10.2174\/138955708783744137","article-title":"The structure activity relationship of discodermolide analogues","volume":"8","author":"Shaw","year":"2008","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Tangutur, A.D., Kumar, D., Krishna, K.V., and Kantevari, S. (2017). Microtubule targeting agents as cancer chemotherapeutics: An overview of molecular hybrids as stabilising and destabilising agents. Curr. Top. Med. Chem.","DOI":"10.2174\/1568026617666170104145640"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"440","DOI":"10.2174\/092986708783503168","article-title":"Chemoprevention of cancer by isothiocyanates and anthocyanins: Mechanisms of action and structure-activity relationship","volume":"15","author":"Fimognari","year":"2008","journal-title":"Curr. Med. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.mrgentox.2006.06.035","article-title":"Genotoxic evaluation of extracts from aplysina fulva, a brazilian marine sponge","volume":"611","author":"Aiub","year":"2006","journal-title":"Mutat. Res."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1093\/mutage\/10.4.357","article-title":"Biotransformation of genotoxic agents in marine sponges. Mechanisms and modulation","volume":"10","author":"Bagnasco","year":"1995","journal-title":"Mutagenesis"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1016\/j.tiv.2008.09.003","article-title":"Genotoxic and antigenotoxic evaluation of extracts from arenosclera brasiliensis, a brazilian marine sponge","volume":"22","author":"Stankevicins","year":"2008","journal-title":"Toxicol. In Vitro"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3109\/01480545.2010.494669","article-title":"Antimicrobial, antioxidant, and antimutagenic activities of selected marine natural products and tobacco cembranoids","volume":"34","author":"Aqil","year":"2011","journal-title":"Drug Chem. Toxicol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/0027-5107(94)90313-1","article-title":"Antimutagens as cancer chemopreventive agents in the diet","volume":"307","author":"Ferguson","year":"1994","journal-title":"Mutat. Res."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.tiv.2005.08.012","article-title":"Investigation of genotoxic and antigenotoxic activities of melampodium divaricatum in salmonella typhimurium","volume":"20","author":"Nogueira","year":"2006","journal-title":"Toxicol. In Vitro"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.mrfmmm.2005.04.018","article-title":"Development of cancer chemopreventive drugs based on mechanistic approaches","volume":"591","author":"Steele","year":"2005","journal-title":"Mutat. Res."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0165-1110(94)90001-9","article-title":"Genotoxicity and carcinogenicity of metronidazole","volume":"317","author":"Dobias","year":"1994","journal-title":"Mutat. Res."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1002\/biot.201300492","article-title":"Three-dimensional models of cancer for pharmacology and cancer cell biology: Capturing tumor complexity in vitro\/ex vivo","volume":"9","author":"Hickman","year":"2014","journal-title":"Biotechnol. J."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S1056-8719(00)00107-6","article-title":"Drug-like properties and the causes of poor solubility and poor permeability","volume":"44","author":"Lipinski","year":"2000","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1351\/pac198658050701","article-title":"Halichondrins-antitumor polyether macrolides from a marine sponge","volume":"58","author":"Hirata","year":"1986","journal-title":"Pure Appl. Chem."},{"key":"ref_199","unstructured":"Drugs.com (2017, July 20). Fda Approves Halaven. Available online: https:\/\/www.drugs.com\/newdrugs\/fda-approves-halaven-late-stage-breast-cancer-2406.html."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4048\/jbc.2016.19.1.8","article-title":"Patient management with eribulin in metastatic breast cancer: A clinical practice guide","volume":"19","author":"Ro","year":"2016","journal-title":"J. Breast Cancer"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1200\/JCO.2014.56.7479","article-title":"Chemotherapy and targeted therapy for women with human epidermal growth factor receptor 2-negative (or unknown) advanced breast cancer: American society of clinical oncology clinical practice guideline","volume":"32","author":"Partridge","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1158\/0008-5472.CAN-10-1874","article-title":"Eribulin induces irreversible mitotic blockade: Implications of cell-based pharmacodynamics for in vivo efficacy under intermittent dosing conditions","volume":"71","author":"Towle","year":"2011","journal-title":"Cancer Res."},{"key":"ref_203","first-page":"1013","article-title":"In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin b","volume":"61","author":"Towle","year":"2001","journal-title":"Cancer Res."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.1365-2613.2009.00651.x","article-title":"Microtubule depolymerizing vascular disrupting agents: Novel therapeutic agents for oncology and other pathologies","volume":"90","author":"Kanthou","year":"2009","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/2045-824X-6-3","article-title":"Eribulin mesylate exerts specific gene expression changes in pericytes and shortens pericyte-driven capillary network in vitro","volume":"6","author":"Agoulnik","year":"2014","journal-title":"Vasc. Cell"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1111\/cas.12488","article-title":"Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models","volume":"105","author":"Funahashi","year":"2014","journal-title":"Cancer Sci."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1158\/1078-0432.CCR-14-3252","article-title":"Eribulin mesylate: Mechanism of action of a unique microtubule-targeting agent","volume":"21","author":"Risinger","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/2001-1326-3-17","article-title":"Clinical significance of epithelial-mesenchymal transition","volume":"3","author":"Steinestel","year":"2014","journal-title":"Clin. Transl. Med."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1038\/bjc.2014.80","article-title":"Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (emt) to mesenchymal-epithelial transition (met) states","volume":"110","author":"Yoshida","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1002\/pbc.24517","article-title":"Initial testing (stage 1) of eribulin, a novel tubulin binding agent, by the pediatric preclinical testing program","volume":"60","author":"Kolb","year":"2013","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_211","first-page":"1611","article-title":"Broad spectrum preclinical antitumor activity of eribulin (halaven(r)): Optimal effectiveness under intermittent dosing conditions","volume":"32","author":"Towle","year":"2012","journal-title":"Anticancer Res."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/S0140-6736(11)60070-6","article-title":"Eribulin monotherapy versus treatment of physician\u2019s choice in patients with metastatic breast cancer (embrace): A phase 3 open-label randomised study","volume":"377","author":"Cortes","year":"2011","journal-title":"Lancet"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1200\/JCO.2013.52.4892","article-title":"Phase iii open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane","volume":"33","author":"Kaufman","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_214","unstructured":"FDA (2017, August 17). Fda Approves First Drug to Show Survival Benefit in Liposarcoma, Available online: https:\/\/www.fda.gov\/newsevents\/newsroom\/pressannouncements\/ucm483714.htm."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1016\/S0140-6736(15)01283-0","article-title":"Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: A randomised, open-label, multicentre, phase 3 trial","volume":"387","author":"Schoffski","year":"2016","journal-title":"Lancet"},{"key":"ref_216","unstructured":"(2017, July 20). ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/results?cond=breast+cancer&term=eribulin+mesylate&cntry1=&state1=&Search=Search."},{"key":"ref_217","unstructured":"(2017, July 23). ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/results?term=eribulin+mesylate&type=&rslt=&age_v=&gndr=&cond=Cancer&intr=&titles=combination&outc=&spons=&lead=&id=&cntry1=&state1=&cntry2=&state2=&cntry3=&state3=&locn=&rcv_s=&rcv_e=&lup_s=&lup_e=."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"4453","DOI":"10.1016\/S0040-4039(00)73382-X","article-title":"Hemiasterlin and geodiamolide ta; two new cytotoxic peptides from the marine sponge Hemiasterella minor (kirkpatrick)","volume":"35","author":"Talpir","year":"1994","journal-title":"Tetrahedron Lett."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.1158\/1535-7163.MCT-09-0301","article-title":"Tubulin-based antimitotic mechanism of e7974, a novel analogue of the marine sponge natural product hemiasterlin","volume":"8","author":"Kuznetsov","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_220","first-page":"810","article-title":"Tubulin-based antimitotic mechanism of novel hemiasterlin analog E7974","volume":"65","author":"Kuznetsov","year":"2005","journal-title":"Proceedings of the 96th Annual Meeting 2005"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"4262","DOI":"10.1002\/cncr.27428","article-title":"A phase 1 trial of e7974 administered on day 1 of a 21-day cycle in patients with advanced solid tumors","volume":"118","author":"Bayraktar","year":"2012","journal-title":"Cancer"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"S74","DOI":"10.1016\/S0959-8049(16)30224-6","article-title":"361 phase i, open-label, dose-escalating clinical and pharmacokinetic study of the novel antimicrotubulin agent pm060184 administered over 10 minutes on days 1\u20133 and 15\u201317 every 28 days to patients with advanced malignant solid tumors","volume":"51","author":"Hidalgo","year":"2015","journal-title":"Eur. J. Cancer"},{"key":"ref_223","unstructured":"FDA (2017, July 25). Guidance for Industry, Available online: https:\/\/www.fda.gov\/downloads\/Drugs\/Guidances\/ucm085389.pdf."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.cbpc.2008.01.005","article-title":"Cytotoxicity and genotoxicity of ingenamine g isolated from the brazilian marine sponge Pachychalina alcaloidifera","volume":"147","author":"Cavalcanti","year":"2008","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/15\/10\/310\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:47:13Z","timestamp":1760208433000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/15\/10\/310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,13]]},"references-count":224,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,10]]}},"alternative-id":["md15100310"],"URL":"https:\/\/doi.org\/10.3390\/md15100310","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,13]]}}}