{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T18:57:18Z","timestamp":1774292238033,"version":"3.50.1"},"reference-count":189,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union Framework Program for Research and Innovation Horizon 2020 through project SponGES","award":["H2020-BG-01-2015-679849"],"award-info":[{"award-number":["H2020-BG-01-2015-679849"]}]},{"name":"European Union Framework Program for Research and Innovation Horizon 2020 through project SponGES","award":["0474_BLUEBIOLAB_1_E"],"award-info":[{"award-number":["0474_BLUEBIOLAB_1_E"]}]},{"name":"European Union Framework Program for Research and Innovation Horizon 2020 through project SponGES","award":["Norte-01-0145-FEDER-000040"],"award-info":[{"award-number":["Norte-01-0145-FEDER-000040"]}]},{"name":"European Regional Development Fund, through INTERREG Espa\u00f1a-Portugal 2014-2020 under BLUEBIOLAB","award":["H2020-BG-01-2015-679849"],"award-info":[{"award-number":["H2020-BG-01-2015-679849"]}]},{"name":"European Regional Development Fund, through INTERREG Espa\u00f1a-Portugal 2014-2020 under BLUEBIOLAB","award":["0474_BLUEBIOLAB_1_E"],"award-info":[{"award-number":["0474_BLUEBIOLAB_1_E"]}]},{"name":"European Regional Development Fund, through INTERREG Espa\u00f1a-Portugal 2014-2020 under BLUEBIOLAB","award":["Norte-01-0145-FEDER-000040"],"award-info":[{"award-number":["Norte-01-0145-FEDER-000040"]}]},{"name":"NORTE2020\/PT2020 Programme under ATLANTIDA","award":["H2020-BG-01-2015-679849"],"award-info":[{"award-number":["H2020-BG-01-2015-679849"]}]},{"name":"NORTE2020\/PT2020 Programme under ATLANTIDA","award":["0474_BLUEBIOLAB_1_E"],"award-info":[{"award-number":["0474_BLUEBIOLAB_1_E"]}]},{"name":"NORTE2020\/PT2020 Programme under ATLANTIDA","award":["Norte-01-0145-FEDER-000040"],"award-info":[{"award-number":["Norte-01-0145-FEDER-000040"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Despite its low prevalence, pancreatic cancer (PC) is one of the deadliest, typically characterised as silent in early stages and with a dramatically poor prognosis when in its advanced stages, commonly associated with a high degree of metastasis. Many efforts have been made in pursuing innovative therapeutical approaches, from the search for new cytotoxic drugs and other bioactive compounds, to the development of more targeted approaches, including improved drug delivery devices. Marine biotechnology has been contributing to this quest by providing new chemical leads and materials originating from different organisms. In this review, marine biodiscovery for PC is addressed, particularly regarding marine invertebrates (namely sponges, molluscs, and bryozoans), seaweeds, fungi, and bacteria. In addition, the development of biomaterials based on marine-originating compounds, particularly chitosan, fucoidan, and alginate, for the production of advanced cancer therapies, is also discussed. The key role that drug delivery can play in new cancer treatments is highlighted, as therapeutical outcomes need to be improved to give further hope to patients.<\/jats:p>","DOI":"10.3390\/md20110689","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T06:01:28Z","timestamp":1667282488000},"page":"689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Marine-Inspired Drugs and Biomaterials in the Perspective of Pancreatic Cancer Therapies"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3627-8173","authenticated-orcid":false,"given":"Andreia S.","family":"Fernandes","sequence":"first","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2013Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, Braga, 4710-057 Guimar\u00e3es, Portugal"}]},{"given":"Catarina","family":"Oliveira","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2013Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, Braga, 4710-057 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4295-6129","authenticated-orcid":false,"given":"Rui L.","family":"Reis","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2013Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, Braga, 4710-057 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3868-0251","authenticated-orcid":false,"given":"Albino","family":"Martins","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2013Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, Braga, 4710-057 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8520-603X","authenticated-orcid":false,"given":"Tiago H.","family":"Silva","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2013Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, Braga, 4710-057 Guimar\u00e3es, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.20546\/ijcmas.2017.605.259","article-title":"Antimicrobial drug discovery: Evident shifting from terrestrial to marine micro-organisms","volume":"6","author":"Singh","year":"2017","journal-title":"Int. J. Curr. Microbiol. Appl. Sci."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","unstructured":"Calcabrini, C., Catanzaro, E., Bishayee, A., Turrini, E., and Fimognari, C. (2017). Marine sponge natural products with anticancer potential: An updated review. Mar. Drugs, 15.","DOI":"10.3390\/md15100310"},{"key":"ref_4","first-page":"8194","article-title":"Tumour heterogeneity and resistance to cancer therapies","volume":"15","author":"Shaw","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.ccr.2005.05.024","article-title":"Therapeutic targeting of the tumor microenvironment","volume":"7","author":"Joyce","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_6","first-page":"894","article-title":"Participation of CCL1 in snail-positive fibroblasts in colorectal cancer contribute to 5-fluorouracil\/paclitaxel chemoresistance","volume":"50","author":"Li","year":"2018","journal-title":"Cancer Res. Treat. Off. J. Korean Cancer Assoc."},{"key":"ref_7","unstructured":"(2020, March 24). Surveillance, Epidemiology, and End Results Program (based on 2008\u20132012 Cases and Deaths), Available online: http:\/\/seer.cancer.gov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3322\/caac.20138","article-title":"Cancer statistics, 2012","volume":"62","author":"Siegel","year":"2012","journal-title":"CA A Cancer J. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14740\/wjon1166","article-title":"Epidemiology of pancreatic cancer: Global trends, etiology and risk factors","volume":"10","author":"Rawla","year":"2019","journal-title":"World J. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nrgastro.2009.177","article-title":"Epidemiology of pancreatic cancer: An overview","volume":"6","author":"Raimondi","year":"2009","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1007\/s00268-003-7165-7","article-title":"Treatment of pancreatic cancer: Challenge of the facts","volume":"27","author":"Beger","year":"2003","journal-title":"World J. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nrgastro.2009.89","article-title":"Pancreatic cancer: Molecular pathogenesis and new therapeutic targets","volume":"6","author":"Wong","year":"2009","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.canlet.2015.11.048","article-title":"The lymphatic system and pancreatic cancer","volume":"381","author":"Fink","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1056\/NEJMoa1011923","article-title":"FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer","volume":"364","author":"Conroy","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nrclinonc.2015.53","article-title":"Pancreatic cancer: From state-of-the-art treatments to promising novel therapies","volume":"12","author":"Hidalgo","year":"2015","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"788","DOI":"10.3892\/mco.2013.131","article-title":"Prognostic factors in metastatic pancreatic cancer: Older patients are associated with reduced overall survival","volume":"1","author":"Tas","year":"2013","journal-title":"Mol. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1200\/JCO.1997.15.6.2403","article-title":"Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial","volume":"15","author":"Burris","year":"1997","journal-title":"J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.bbamcr.2014.10.003","article-title":"Mutant p53 stimulates chemoresistance of pancreatic adenocarcinoma cells to gemcitabine","volume":"1853","author":"Fiorini","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1038\/onc.2013.357","article-title":"Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase","volume":"33","author":"Weizman","year":"2014","journal-title":"Oncogene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1158\/1078-0432.CCR-07-2247","article-title":"Gemcitabine resistance in pancreatic cancer: Picking the key players","volume":"2008","author":"Kim","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Glassman, D.C., Palmaira, R.L., Covington, C.M., Desai, A.M., Ku, G.Y., Li, J., and Kenneth, H.Y. (2018). Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4605-1"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1200\/JCO.2006.10.2111","article-title":"Gemcitabine, cisplatin, and radiotherapy for patients with locally advanced pancreatic adenocarcinoma: Results of the North Central Cancer Treatment Group Phase II Study N9942","volume":"25","author":"Haddock","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_23","first-page":"310","article-title":"Updates of adjuvant therapy in pancreatic cancer: Where are we and where are we going?","volume":"11","author":"Li","year":"2010","journal-title":"JOP J. Pancreas"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Amrutkar, M., and Gladhaug, I.P. (2017). Pancreatic cancer chemoresistance to gemcitabine. Cancers, 9.","DOI":"10.3390\/cancers9110157"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e01055","DOI":"10.1016\/j.heliyon.2018.e01055","article-title":"Pancreatic cancer chemo-resistance is driven by tumor phenotype rather than tumor genotype","volume":"4","author":"Swayden","year":"2018","journal-title":"Heliyon"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.3748\/wjg.v20.i9.2237","article-title":"Pancreatic cancer stroma: Understanding biology leads to new therapeutic strategies","volume":"20","author":"Rucki","year":"2014","journal-title":"World J. Gastroenterol. WJG"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.ccr.2012.01.007","article-title":"Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma","volume":"21","author":"Provenzano","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1136\/gutjnl-2012-302604","article-title":"Improving drug delivery to pancreatic cancer: Breaching the stromal fortress by targeting hyaluronic acid","volume":"61","author":"Michl","year":"2012","journal-title":"Gut"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nnano.2012.45","article-title":"Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner","volume":"7","author":"Chauhan","year":"2012","journal-title":"Nat. Nanotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1053\/j.gastro.2015.07.058","article-title":"Signal transducer and activator of transcription 3, mediated remodeling of the tumor microenvironment results in enhanced tumor drug delivery in a mouse model of pancreatic cancer","volume":"149","author":"Nagathihalli","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1053\/j.gastro.2016.03.010","article-title":"Loss of P53 function activates JAK2\u2013STAT3 signaling to promote pancreatic tumor growth, stroma modification, and gemcitabine resistance in mice and is associated with patient survival","volume":"151","author":"Song","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms3516","article-title":"Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels","volume":"4","author":"Chauhan","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"eaai8504","DOI":"10.1126\/scitranslmed.aai8504","article-title":"Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis","volume":"9","author":"Vennin","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/nrgastro.2010.179","article-title":"High stromal expression of \u03b1-smooth-muscle actin correlates with aggressive pancreatic cancer biology","volume":"7","author":"Nanda","year":"2010","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_35","first-page":"2057","article-title":"Pancreatic stellate cells facilitate pancreatic cancer cell viability and invasion","volume":"17","author":"Liu","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"172","DOI":"10.4252\/wjsc.v10.i11.172","article-title":"Pancreatic cancer stem cells: Perspectives on potential therapeutic approaches of pancreatic ductal adenocarcinoma","volume":"10","author":"Brandi","year":"2018","journal-title":"World J. Stem Cells"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.stem.2015.02.015","article-title":"The cancer stem cell niche: How essential is the niche in regulating stemness of tumor cells?","volume":"16","author":"Plaks","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Valle, S., Martin-Hijano, L., Alcal\u00e1, S., Alonso-Nocelo, M., and Sainz, B. (2018). The ever-evolving concept of the cancer stem cell in pancreatic cancer. Cancers, 10.","DOI":"10.3390\/cancers10020033"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.canlet.2017.02.012","article-title":"Targeting autophagy in cancer stem cells as an anticancer therapy","volume":"393","author":"Lei","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"547","DOI":"10.4252\/wjsc.v7.i3.547","article-title":"New insights into pancreatic cancer stem cells","volume":"7","author":"Rao","year":"2015","journal-title":"World J. Stem Cells"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0014-5793(00)01181-9","article-title":"ERK activation upon hypoxia: Involvement in HIF-1 activation","volume":"468","author":"Minet","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/s11033-015-3858-x","article-title":"Cancer metabolism and the Warburg effect: The role of HIF-1 and PI3K","volume":"42","author":"Courtnay","year":"2015","journal-title":"Mol. Biol. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/bjc.2015.284","article-title":"Analysis of the intra-and intertumoral heterogeneity of hypoxia in pancreatic cancer patients receiving the nitroimidazole tracer pimonidazole","volume":"113","author":"Dhani","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1111\/jcmm.14896","article-title":"PTBP3 promotes malignancy and hypoxia-induced chemoresistance in pancreatic cancer cells by ATG12 up-regulation","volume":"24","author":"Ma","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1148\/86.3.470","article-title":"Arteriographic diagnosis of pancreatic lesions","volume":"86","author":"Ranniger","year":"1966","journal-title":"Radiology"},{"key":"ref_46","first-page":"7298","article-title":"Generation of multiple angiogenesis inhibitors by human pancreatic cancer","volume":"61","author":"Kisker","year":"2001","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1002\/ijc.27715","article-title":"Persistent activation of pancreatic stellate cells creates a microenvironment favorable for the malignant behavior of pancreatic ductal adenocarcinoma","volume":"132","author":"Tang","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1158\/1541-7786.MCR-10-0139","article-title":"Mechanisms of motility in metastasizing cells","volume":"8","author":"Yilmaz","year":"2010","journal-title":"Mol. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1158\/0008-5472.CAN-13-3009","article-title":"Hypoxia-inducible factor-1 promotes pancreatic ductal adenocarcinoma invasion and metastasis by activating transcription of the actin-bundling protein fascin","volume":"74","author":"Zhao","year":"2014","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1586\/17474124.2016.1117386","article-title":"The role of hypoxia in pancreatic cancer: A potential therapeutic target?","volume":"10","author":"Erkan","year":"2016","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2147\/HP.S93413","article-title":"The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy","volume":"3","author":"Muz","year":"2015","journal-title":"Hypoxia"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Khalifa, S.A., Elias, N., Farag, M.A., Chen, L., Saeed, A., Hegazy, M.E.F., and Chang, F.R. (2019). Marine natural products: A source of novel anticancer drugs. Mar. Drugs, 17.","DOI":"10.3390\/md17090491"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Han, B.N., Hong, L.L., Gu, B.B., Sun, Y.T., Wang, J., Liu, J.T., and Lin, H.W. (2019). Natural Products from Sponges. Symbiotic Microbiomes of Coral Reefs Sponges and Corals, Springer.","DOI":"10.1007\/978-94-024-1612-1_15"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1021\/acs.jnatprod.5b01055","article-title":"Natural products as sources of new drugs from 1981 to 2014","volume":"79","author":"Newman","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/BF00763625","article-title":"Cytotoxic activity of aaptamines from suberitid marine sponges","volume":"22","author":"Fedoreev","year":"1988","journal-title":"Pharm. Chem. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0021-9150(00)00553-0","article-title":"Selective inhibition by probucol of vascular cell adhesion molecule-1 (VCAM-1) expression in human vascular endothelial cells","volume":"155","author":"Markiewski","year":"2001","journal-title":"Atherosclerosis"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5565","DOI":"10.1021\/jo9824448","article-title":"Adociasulfates 1\u2212 6, Inhibitors of Kinesin Motor Proteins from the Sponge Haliclona (aka Adocia) sp.","volume":"64","author":"Blackburn","year":"1999","journal-title":"J. Org. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"347","DOI":"10.4062\/biomolther.2016.067","article-title":"Marine sponges as a drug treasure","volume":"24","author":"Anjum","year":"2016","journal-title":"Biomol. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1021\/jo00288a037","article-title":"Antiviral and antitumor agents from a New Zealand sponge, Mycale sp. 2. Structures and solution conformations of mycalamides A and B","volume":"55","author":"Perry","year":"1990","journal-title":"J. Org. Chem."},{"key":"ref_60","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_61","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":"Harmody","year":"2017","journal-title":"Anti-Cancer Drugs"},{"key":"ref_62","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_63","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_64","doi-asserted-by":"crossref","first-page":"4964","DOI":"10.1021\/jo00303a043","article-title":"Isobatzellines A, B, C, and D. Cytotoxic and antifungal pyrroloquinoline alkaloids from the marine sponge Batzella sp.","volume":"55","author":"Sun","year":"1990","journal-title":"J. Org. Chem."},{"key":"ref_65","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":"Johnson","year":"2009","journal-title":"Anti-Cancer Drugs"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7631","DOI":"10.1021\/ja00096a020","article-title":"Microsclerodermins A and B. Antifungal cyclic peptides from the lithistid sponge Microscleroderma sp.","volume":"116","author":"Bewley","year":"1994","journal-title":"J. Am. Chem. Soc."},{"key":"ref_67","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":"Maers","year":"2015","journal-title":"Investig. New Drugs"},{"key":"ref_68","unstructured":"Wright, A.E., Pomponi, S.A., Longley, R.E., and Isbrucker, R.A. (2002). Antiproliferative Activity of Microsclerodermins. (No. 6,384,187), U.S. Patent."},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1002\/med.21423","article-title":"Marine Mollusk-Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance","volume":"37","author":"Ciavatta","year":"2017","journal-title":"Med. Res. Rev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s10637-005-2909-x","article-title":"Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers","volume":"23","author":"Kindler","year":"2005","journal-title":"Investig. New Drugs"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"944","DOI":"10.3390\/md11030944","article-title":"Predictive factors of sensitivity to elisidepsin, a novel Kahalalide F-derived marine compound","volume":"11","author":"Serova","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1038\/modpathol.2011.74","article-title":"Loss of E-cadherin expression and outcome among patients with resectable pancreatic adenocarcinomas","volume":"24","author":"Hong","year":"2011","journal-title":"Mod. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Figuerola, B., and Avila, C. (2019). The Phylum Bryozoa as a promising source of anticancer drugs. Mar. Drugs, 17.","DOI":"10.20944\/preprints201906.0029.v1"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1021\/np980410p","article-title":"Amathaspiramides A\u2212 F, Novel Brominated Alkaloids from the Marine Bryozoan Amathia wilsoni","volume":"62","author":"Morris","year":"1999","journal-title":"J. Nat. Prod."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1248\/cpb.c16-00256","article-title":"Antiproliferative activity of amathaspiramide alkaloids and analogs","volume":"64","author":"Shimokawa","year":"2016","journal-title":"Chem. Pharm. Bull."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.4314\/tjpr.v15i10.3","article-title":"Bryostatin I inhibits growth and proliferation of pancreatic cancer cells via suppression of NF-\u03baB activation","volume":"15","author":"Peng","year":"2016","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/COC.0b013e3181a31920","article-title":"Phase II study of paclitaxel plus the protein kinase C inhibitor bryostatin-1 in advanced pancreatic carcinoma","volume":"33","author":"Lam","year":"2010","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3109\/13880209.2013.804100","article-title":"Marine natural products: Bryostatins in preclinical and clinical studies","volume":"52","author":"Rajchard","year":"2014","journal-title":"Pharm. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7059","DOI":"10.1158\/1078-0432.CCR-06-1419","article-title":"Phase I study of bryostatin 1 and gemcitabine","volume":"12","author":"Gadgeel","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.2174\/092986712800493020","article-title":"The chemistry and biology of the bryostatins: Potential PKC inhibitors in clinical development","volume":"19","author":"Ruan","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Leandro, A., Pereira, L., and Gon\u00e7alves, A.M. (2020). Diverse applications of marine macroalgae. Mar. Drugs, 18.","DOI":"10.3390\/md18010017"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Rocha, D.H., Seca, A.M., and Pinto, D.C. (2018). Seaweed secondary metabolites in vitro and in vivo anticancer activity. Mar. Drugs, 16.","DOI":"10.3390\/md16110410"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3389\/fphar.2018.00777","article-title":"From marine origin to therapeutics: The antitumor potential of marine algae-derived compounds","volume":"9","author":"Alves","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Peng, Y., Hu, J., Yang, B., Lin, X.P., Zhou, X.F., Yang, X.W., and Liu, Y. (2015). Chemical composition of seaweeds. Seaweed Sustainability, Academic Press.","DOI":"10.1016\/B978-0-12-418697-2.00005-2"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"604787","DOI":"10.1155\/2013\/604787","article-title":"Antioxidant, antiproliferative, and antiangiogenesis effects of polyphenol-rich seaweed (Sargassum muticum)","volume":"2013","author":"Namvar","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1021\/acs.biomac.0c00482","article-title":"Fucoidan immobilized at the surface of a fibrous mesh presents toxic effects over melanoma cells, but not over non-cancer skin cells","volume":"21","author":"Oliveira","year":"2020","journal-title":"Biomacromolecules"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-55309-1","article-title":"Antioxidant, Anticancer Activity and Phytochemical Analysis of Green Algae, Chaetomorpha Collected from the Arabian Gulf","volume":"9","author":"Haq","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Saadaoui, I., Rasheed, R., Abdulrahman, N., Bounnit, T., Cherif, M., Al Jabri, H., and Mraiche, F. (2020). Algae-Derived Bioactive Compounds with Anti-Lung Cancer Potential. Mar. Drugs, 18.","DOI":"10.3390\/md18040197"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.ijbiomac.2019.07.127","article-title":"In vitro anticancer activity of fucoidan extracted from Sargassum cinereum against Caco-2 cells","volume":"138","author":"Narayani","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.ijbiomac.2018.06.054","article-title":"Anti-inflammatory effect of low molecular weight fucoidan from Saccharina japonica on atherosclerosis in apoE-knockout mice","volume":"118","author":"Xu","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Kan, J., Hood, M., Burns, C., Scholten, J., Chuang, J., Tian, F., and Gui, M. (2017). A novel combination of wheat peptides and fucoidan attenuates ethanol-induced gastric mucosal damage through anti-oxidant, anti-inflammatory, and pro-survival mechanisms. Nutrients, 9.","DOI":"10.3390\/nu9090978"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"115034","DOI":"10.1016\/j.carbpol.2019.115034","article-title":"Fucoidan from Fucus vesiculosus inhibits new blood vessel formation and breast tumor growth in vivo","volume":"223","author":"Oliveira","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Van Weelden, G., Bobi\u0144ski, M., Ok\u0142a, K., Van Weelden, W.J., Romano, A., and Pijnenborg, J. (2019). Fucoidan structure and activity in relation to anti-cancer mechanisms. Mar. Drugs, 17.","DOI":"10.3390\/md17010032"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"112078","DOI":"10.1016\/j.phytochem.2019.112078","article-title":"Fucoidan from marine brown algae attenuates pancreatic cancer progression by regulating p53\u2013NF\u03baB crosstalk","volume":"167","author":"Delma","year":"2019","journal-title":"Phytochemistry"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.ijbiomac.2014.12.031","article-title":"Fucoidan from Turbinaria conoides: A multifaceted \u2018deliverable\u2019 to combat pancreatic cancer progression","volume":"74","author":"Delma","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Guzm\u00e1n, M., Rodr\u00edguez-Nogales, A., Algieri, F., and G\u00e1lvez, J. (2018). Potential role of seaweed polyphenols in cardiovascular-associated disorders. Mar. Drugs, 16.","DOI":"10.3390\/md16080250"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.3390\/nu2111106","article-title":"Polyphenols and human health: Prevention of disease and mechanisms of action","volume":"2","author":"Vauzour","year":"2010","journal-title":"Nutrients"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/ajcn\/88.1.38","article-title":"Flavonoids, flavonoid-rich foods, and cardiovascular risk: A meta-analysis of randomized controlled trials","volume":"88","author":"Hooper","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Renaud, J., and Martinoli, M.G. (2019). Considerations for the use of polyphenols as therapies in neurodegenerative diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081883"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Abdal Dayem, A., Choi, H.Y., Yang, G.M., Kim, K., Saha, S.K., and Cho, S.G. (2016). The anti-cancer effect of polyphenols against breast cancer and cancer stem cells: Molecular mechanisms. Nutrients, 8.","DOI":"10.3390\/nu8090581"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jfda.2016.01.005","article-title":"Inhibitory effects of polyphenol-enriched extract from Ziyang tea against human breast cancer MCF-7 cells through reactive oxygen species-dependent mitochondria molecular mechanism","volume":"24","author":"Li","year":"2016","journal-title":"J. Food Drug Anal."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.fct.2006.02.002","article-title":"Antioxidant and antiproliferative activities of extracts from a variety of edible seaweeds","volume":"44","author":"Yuan","year":"2006","journal-title":"Food Chem. Toxicol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1007\/s10811-019-02016-z","article-title":"The cytotoxic activity of extracts of the brown alga Cystoseira tamariscifolia (Hudson) Papenfuss, against cancer cell lines changes seasonally","volume":"32","author":"Mansur","year":"2020","journal-title":"J. Appl. Phycol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Aravindan, S., Delma, C.R., Thirugnanasambandan, S.S., Herman, T.S., and Aravindan, N. (2013). Anti-pancreatic cancer deliverables from sea: First-hand evidence on the efficacy, molecular targets and mode of action for multifarious polyphenols from five different brown-algae. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061977"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s13287-015-0173-3","article-title":"Polyphenols from marine brown algae target radiotherapy-coordinated EMT and stemness-maintenance in residual pancreatic cancer","volume":"6","author":"Aravindan","year":"2015","journal-title":"Stem Cell Res. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5717","DOI":"10.18632\/oncotarget.13900","article-title":"Hormophysa triquerta polyphenol, an elixir that deters CXCR4-and COX2-dependent dissemination destiny of treatment-resistant pancreatic cancer cells","volume":"8","author":"Aravindan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12929-015-0132-4","article-title":"Novel adjuvants from seaweed impede autophagy signaling in therapy-resistant residual pancreatic cancer","volume":"22","author":"Aravindan","year":"2015","journal-title":"J. Biomed. Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s11010-019-03579-8","article-title":"Targeting acquired oncogenic burden in resilient pancreatic cancer: A novel benefit from marine polyphenols","volume":"460","author":"Aravindan","year":"2019","journal-title":"Mol. Cell. Biochem."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Singh, A.K., Rana, H.K., and Pandey, A.K. (2019). Fungal-Derived Natural Product: Synthesis, Function, and Applications. Recent Advancement in White Biotechnology Through Fungi, Springer.","DOI":"10.1007\/978-3-030-14846-1_8"},{"key":"ref_111","first-page":"269","article-title":"Marine-derived fungi: Diversity of enzymes and biotechnological applications","volume":"6","author":"Passarini","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1146\/annurev-marine-120710-100802","article-title":"Marine fungi: Their ecology and molecular diversity","volume":"4","author":"Richards","year":"2012","journal-title":"Annu. Rev. Mar. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Agrawal, D., and Dhanasekaran, M. (2019). Recent progress in research on the pharmacological potential of mushrooms and prospects for their clinical application. Medicinal Mushrooms, Springer.","DOI":"10.1007\/978-981-13-6382-5"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.apjtm.2015.09.005","article-title":"Potential of four marine-derived fungi extracts as anti-proliferative and cell death-inducing agents in seven human cancer cell lines","volume":"8","author":"Ramos","year":"2015","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Malh\u00e3o, F., Ramos, A.A., Buttachon, S., Dethoup, T., Kijjoa, A., and Rocha, E. (2019). Cytotoxic and antiproliferative effects of preussin, a hydroxypyrrolidine derivative from the marine sponge-associated fungus Aspergillus candidus KUFA 0062, in a panel of breast cancer cell lines and using 2D and 3D cultures. Mar. Drugs, 17.","DOI":"10.3390\/md17080448"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1021\/np070580e","article-title":"Scopularides A and B, cyclodepsipeptides from a marine sponge-derived fungus, Scopulariopsis brevicaulis","volume":"71","author":"Yu","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.3390\/md12063203","article-title":"Zn-driven discovery of a hydrothermal vent fungal metabolite clavatustide C, and an experimental study of the anti-cancer mechanism of clavatustide B","volume":"12","author":"Ye","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_118","first-page":"73","article-title":"Sansalvamide induces pancreatic cancer growth arrest through changes in the cell cycle","volume":"30","author":"Heiferman","year":"2010","journal-title":"Anticancer. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1097\/01.mpa.0000193785.26970.13","article-title":"Pancreatic cancer cell cycle arrest and apoptosis are induced by a novel depsipeptide sansalvamide analogue","volume":"31","author":"Ujiki","year":"2005","journal-title":"Pancreas"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Zhang, W., Zhu, Y., Yu, H., Liu, X., Jiao, B., and Lu, X. (2021). Libertellenone H, a natural pimarane diterpenoid, inhibits thioredoxin system and induces ROS-mediated apoptosis in human pancreatic cancer cells. Molecules, 26.","DOI":"10.3390\/molecules26020315"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3390\/cancers2020209","article-title":"Thioredoxin and cancer: A role for thioredoxin in all states of tumor oxygenation","volume":"2","author":"Karlenius","year":"2010","journal-title":"Cancers"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"10175","DOI":"10.1002\/chem.201905792","article-title":"The thioredoxin system: A promising target for cancer drug development","volume":"26","author":"Ghareeb","year":"2020","journal-title":"Chem.\u2013Eur. J."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"5903","DOI":"10.1016\/j.bmc.2018.10.040","article-title":"Butenolides from a marine-derived fungus Aspergillus terreus with antitumor activities against pancreatic ductal adenocarcinoma cells","volume":"26","author":"Qi","year":"2018","journal-title":"Bioorganic Med. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.tibtech.2008.10.005","article-title":"Panning for chemical gold: Marine bacteria as a source of new therapeutics","volume":"27","author":"Williams","year":"2009","journal-title":"Trends Biotechnol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/sj.jim.7000025","article-title":"Myxobacteria, producers of novel bioactive substances","volume":"27","author":"Reichenbach","year":"2001","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Wang, C., Fan, Q., Zhang, X., Lu, X., Xu, Y., Zhu, W., and Hao, L. (2018). Isolation, characterization, and pharmaceutical applications of an exopolysaccharide from Aerococcus uriaeequi. Mar. Drugs, 16.","DOI":"10.3390\/md16090337"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3389\/fchem.2018.00498","article-title":"Coculture of marine Streptomyces sp. with Bacillus sp. produces a new piperazic acid-bearing cyclic peptide","volume":"6","author":"Shin","year":"2018","journal-title":"Front. Chem."},{"key":"ref_128","first-page":"fny202","article-title":"Bacillus and Virgibacillus strains isolated from three Mexican coasts antagonize Staphylococcus aureus and Vibrio parahaemolyticus","volume":"365","year":"2018","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"5418","DOI":"10.1021\/ja010453j","article-title":"Total structure determination of apratoxin A, a potent novel cytotoxin from the marine cyanobacterium Lyngbya majuscula","volume":"123","author":"Luesch","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1021\/ja7110064","article-title":"Structure and activity of largazole, a potent antiproliferative agent from the Floridian marine cyanobacterium Symploca sp.","volume":"130","author":"Taori","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1002\/anie.200705295","article-title":"Proximicins A, B, and C\u2014Antitumor furan analogues of netropsin from the marine actinomycete Verrucosispora induce upregulation of p53 and the cyclin kinase inhibitor p21","volume":"47","author":"Schneider","year":"2008","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"4729","DOI":"10.1021\/ja00090a020","article-title":"Total structures of cryptophycins, potent antitumor depsipeptides from the blue-green alga Nostoc sp. strain GSV 224","volume":"116","author":"Trimurtulu","year":"1994","journal-title":"J. Am. Chem. Soc."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1021\/np800121a","article-title":"Apratoxin D, a potent cytotoxic cyclodepsipeptide from Papua New Guinea collections of the marine cyanobacteria Lyngbya majuscula and Lyngbya sordida","volume":"71","author":"Suyama","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1158\/1535-7163.MCT-15-0648","article-title":"Apratoxin A Shows Novel Pancreas-Targeting Activity through the Binding of Sec 61Apratoxin A, a Novel Pancreas-Targeting Agent","volume":"15","author":"Huang","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/nchembio769","article-title":"A functional genomics approach to the mode of action of apratoxin A","volume":"2","author":"Luesch","year":"2006","journal-title":"Nat. Chem. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1021\/ml200176m","article-title":"Systematic chemical mutagenesis identifies a potent novel apratoxin A\/E hybrid with improved in vivo antitumor activity","volume":"2","author":"Chen","year":"2011","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1021\/acsmedchemlett.7b00192","article-title":"Apratoxin S10, a dual inhibitor of angiogenesis and cancer cell growth to treat highly vascularized tumors","volume":"8","author":"Cai","year":"2017","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1124\/mol.109.056085","article-title":"Apratoxin a reversibly inhibits the secretory pathway by preventing cotranslational translocation","volume":"76","author":"Liu","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s10637-018-0647-0","article-title":"Development of apratoxin S10 (Apra S10) as an anti-pancreatic cancer agent and its preliminary evaluation in an orthotopic patient-derived xenograft (PDX) model","volume":"37","author":"Cai","year":"2019","journal-title":"Investig. New Drugs"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.bbrc.2021.01.112","article-title":"Coibamide A kills cancer cells through inhibiting autophagy","volume":"547","author":"Shi","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_141","first-page":"1847","article-title":"Antitumor exopolysaccharides derived from novel marine bacillus: Isolation, characterization aspect and biological activity","volume":"18","author":"Abdelnasser","year":"2017","journal-title":"Asian Pac. J. Cancer Prev. APJCP"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"101133","DOI":"10.1016\/j.jbc.2021.101133","article-title":"Marine bacterial exopolysaccharide EPS11 inhibits migration and invasion of liver cancer cells by directly targeting collagen I","volume":"297","author":"Liu","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1097\/MPA.0b013e3181b9dfda","article-title":"Promotion of tumor cell migration by extracellular matrix proteins in human pancreatic cancer","volume":"38","author":"Ryschich","year":"2009","journal-title":"Pancreas"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1002\/ijc.25942","article-title":"Knockdown of the \u03b21 integrin subunit reduces primary tumor growth and inhibits pancreatic cancer metastasis","volume":"129","author":"Grzesiak","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.carbpol.2017.12.009","article-title":"Biological activities and pharmaceutical applications of polysaccharide from natural resources: A review","volume":"183","author":"Yu","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/00000421-200008000-00022","article-title":"Cisplatin, cytarabine, caffeine, and continuously infused 5-fluorouracil (PACE) in the treatment of advanced pancreatic carcinoma: A phase II study","volume":"23","author":"Ahmed","year":"2000","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1001\/jama.2010.1275","article-title":"Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: A randomized controlled trial","volume":"304","author":"Neoptolemos","year":"2010","journal-title":"JAMA"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s10637-011-9673-x","article-title":"A phase II study of the halichondrin B analog eribulin mesylate in gemcitabine refractory advanced pancreatic cancer","volume":"30","author":"Renouf","year":"2012","journal-title":"Investig. New Drugs"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00280-015-2932-3","article-title":"Phase II trial of salvage therapy with trabectedin in metastatic pancreatic adenocarcinoma","volume":"77","author":"Belli","year":"2016","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_150","unstructured":"National Library of Medicine (U.S.) (2022, October 19). (14 June 2022). Lurbinectedin in Patients with Advanced Pancreatic Cancer with DNA Repair Mutations. Identifier: NCT05229588, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT05229588."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1007\/s10637-011-9766-6","article-title":"Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination","volume":"30","author":"Millward","year":"2012","journal-title":"Investig. New Drugs"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1158\/1078-0432.CCR-19-4042","article-title":"A Randomized Phase II Preoperative Study of Autophagy Inhibition With High-Dose Hydroxychloroquine and Gemcita-bine\/Nab-Paclitaxel in Pancreatic Cancer Patients","volume":"26","author":"Normolle","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S2468-1253(19)30327-9","article-title":"Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): A multicentre, open-label phase 2 study","volume":"5","author":"Philip","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1758835920915978","article-title":"Polymer nanoparticle-assisted chemotherapy of pancreatic cancer","volume":"12","author":"Su","year":"2020","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"228","DOI":"10.20892\/j.issn.2095-3941.2017.0052","article-title":"Recent progress on nanoparticle-based drug delivery systems for cancer therapy","volume":"14","author":"Xin","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.2217\/nnm-2017-0101","article-title":"Complex effects of tumor microenvironment on the tumor disposition of carrier-mediated agents","volume":"12","author":"Lucas","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12951-018-0392-8","article-title":"Nano based drug delivery systems: Recent developments and future prospects","volume":"16","author":"Patra","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.addr.2018.07.007","article-title":"Tumor targeting via EPR: Strategies to enhance patient responses","volume":"130","author":"Golombek","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Yoo, J., Park, C., Yi, G., Lee, D., and Koo, H. (2019). Active targeting strategies using biological ligands for nanoparticle drug delivery systems. Cancers, 11.","DOI":"10.3390\/cancers11050640"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.yexmp.2008.12.004","article-title":"Nanoparticle-based targeted drug delivery","volume":"86","author":"Singh","year":"2009","journal-title":"Exp. Mol. Pathol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1208\/s12249-010-9393-0","article-title":"Chitosan and glyceryl monooleate nanostructures containing gemcitabine: Potential delivery system for pancreatic cancer treatment","volume":"11","author":"Trickler","year":"2010","journal-title":"Aaps Pharmscitech"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.nano.2011.03.009","article-title":"Enhanced antiproliferative activity of Herceptin (HER2)-conjugated gemcitabine-loaded chitosan nanoparticle in pancreatic cancer therapy","volume":"7","author":"Arya","year":"2011","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"259","DOI":"10.3904\/kjim.2002.17.4.259","article-title":"Gemcitabine therapy in patients with advanced pancreatic cancer","volume":"17","author":"Min","year":"2002","journal-title":"Korean J. Intern. Med."},{"key":"ref_164","first-page":"527","article-title":"Folate-chitosan-gemcitabine core-shell nanoparticles targeted to pancreatic cancer","volume":"25","author":"Zhou","year":"2013","journal-title":"Chin. J. Cancer Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1007\/s11095-014-1425-0","article-title":"In vitro and in vivo biological evaluation of O-carboxymethyl chitosan encapsulated metformin nanoparticles for pancreatic cancer therapy","volume":"31","author":"Snima","year":"2014","journal-title":"Pharm. Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.2147\/IJN.S106736","article-title":"Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB\/c mice","volume":"11","author":"Thakkar","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.colsurfb.2015.08.038","article-title":"Dual drug loaded chitosan nanoparticles\u2014Sugar-coated arsenal against pancreatic cancer","volume":"135","author":"David","year":"2015","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.biopha.2018.03.101","article-title":"Evaluation of curcumin loaded chitosan\/PEG blended PLGA nanoparticles for effective treatment of pancreatic cancer","volume":"102","author":"Arya","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Shin, S.W., Jung, W., Choi, C., Kim, S.Y., Son, A., Kim, H., and Park, H.C. (2018). Fucoidan-manganese dioxide nanoparticles potentiate radiation therapy by co-targeting tumor hypoxia and angiogenesis. Mar. Drugs, 16.","DOI":"10.3390\/md16120510"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.ijpharm.2014.07.046","article-title":"Enhancement of phototoxicity against human pancreatic cancer cells with photosensitizer-encapsulated amphiphilic sodium alginate derivative nanoparticles","volume":"473","author":"Yu","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.pan.2017.06.001","article-title":"Preparation and in vitro assessment of wet-spun gemcitabine-loaded polymeric fibers: Towards localized drug delivery for the treatment of pancreatic cancer","volume":"17","author":"Wade","year":"2017","journal-title":"Pancreatology"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"526963","DOI":"10.1155\/2009\/526963","article-title":"Anti-EGFR therapy: Mechanism and advances in clinical efficacy in breast cancer","volume":"2009","author":"Flynn","year":"2009","journal-title":"J. Oncol."},{"key":"ref_173","first-page":"1613","article-title":"Gemcitabine conjugated chitosan and double antibodies (Abc-GC-gemcitabine nanoparticles) enhanced cytoplasmic uptake of gemcitabine and inhibit proliferation and metastasis in human SW1990 pancreatic cancer cells","volume":"23","author":"Xiao","year":"2017","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.ijbiomac.2019.12.177","article-title":"Novel fucoidan based bioactive targeted nanoparticles from Undaria pinnatifida for treatment of pancreatic cancer","volume":"145","author":"Etman","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"405","DOI":"10.21037\/jgo.2016.11.15","article-title":"Predictive and prognostic biomarkers in personalized gastrointestinal cancer treatment","volume":"8","author":"Verdaguer","year":"2017","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1016\/j.biopha.2018.11.097","article-title":"The arrival of predictive biomarkers for monitoring therapy response to natural compounds in cancer drug discovery","volume":"109","author":"Atanasov","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/S2468-1253(19)30175-X","article-title":"Precision medicine in pancreatic cancer: Treating every patient as an exception","volume":"4","author":"Herbst","year":"2019","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.jcmgh.2017.12.004","article-title":"Pancreas 3D organoids: Current and future aspects as a research platform for personalized medicine in pancreatic cancer","volume":"5","author":"Moreira","year":"2018","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Carvalho, A.M., Marques, A.P., Silva, T.H., and Reis, R.L. (2018). Evaluation of the potential of collagen from codfish skin as a biomaterial for biomedical applications. Mar. Drugs, 16.","DOI":"10.3390\/md16120495"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"045004","DOI":"10.1088\/1748-6041\/11\/4\/045004","article-title":"In vitro bioactivity studies of ceramic structures isolated from marine sponges","volume":"11","author":"Barros","year":"2016","journal-title":"Biomed. Mater."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Neves, N.M., and Reis, R.L. (2016). Marine collagen isolation and processing envisaging biomedical applications. Biomaterials from Nature for Advanced Devices and Therapies, Wiley.","DOI":"10.1002\/9781119126218"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10856-019-6234-x","article-title":"Collagen-based bioinks for hard tissue engineering applications: A comprehensive review","volume":"30","author":"Marques","year":"2019","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3389\/fbioe.2019.00343","article-title":"Marine collagen substrates for 2D and 3D ovarian cancer cell systems","volume":"7","author":"Paradiso","year":"2019","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.7150\/thno.42441","article-title":"3D approaches to model the tumor microenvironment of pancreatic cancer","volume":"10","author":"Kieler","year":"2020","journal-title":"Theranostics"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"102016","DOI":"10.1016\/j.ctrv.2020.102016","article-title":"Immunotherapy for pancreatic cancer: A 2020 update","volume":"86","author":"Schizas","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1097\/SLA.0000000000004669","article-title":"A phase 3 randomized clinical trial of chemotherapy with or without algenpantucel-L (hyperacute-pancreas) immunotherapy in subjects with borderline resectable or locally advanced unresectable pancreatic cancer","volume":"275","author":"Hewitt","year":"2022","journal-title":"Ann. Surg."},{"key":"ref_187","unstructured":"National Library of Medicine (U.S.) (2022, October 19). 18 May 2020\u2013Present. Nivolumab and Ipilimumab and Radiation Therapy in Metastatic, Microsatellite Stable Pancreatic Cancer. Clinical Trial Identifier: NCT04361162, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04361162."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"111091","DOI":"10.1016\/j.biopha.2020.111091","article-title":"Marine-derived drugs: Recent advances in cancer therapy and immune signaling","volume":"134","author":"Saeed","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Amer, N.F., and Knaan, T.L. (2022). Natural Products of Marine Origin for the Treatment of Colorectal and Pancreatic Cancers: Mechanisms and Potential. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23148048"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/11\/689\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:07:14Z","timestamp":1760144834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/11\/689"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":189,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["md20110689"],"URL":"https:\/\/doi.org\/10.3390\/md20110689","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,1]]}}}