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stromelysins, gelatinases and membrane-type metalloproteinases. They are involved in the remodelling and turnover of the extracellular matrix proteins. They play a role in wound healing and the pathogenesis of arthritis. In malignancies they play a role in tumor invasion, metastasis and angiogenesis. A number of synthetic matrix metalloproteinase inhibitors (MMPIs) have been developed for clinical use. In preclinical tumor models they have shown promising activity in achieving inhibition of MMPs and reducing tumor growth and metastatic spread. Some have also shown additive or synergistic effects with cytotoxic agents. Phase I and II studies in human subjects have defined the main side effects of these agents as being musculoskeletal pains or arthralgias. As they are cytostatic agents rather than cytotoxic in activity conventional measurements of radiological response for assessment are not applicable in trials. Biological activity has been demonstrated in certain cancers by the effects on levels of tumor markers as surrogate markers of tumor response and also by a fibrotic stromal reaction seen in tumor tissue. Newer agents have been developed with selective inhibition of certain MMPs in an attempt to reduce the side effects. A number of phase III human clinical trials evaluating MMPs are being carried out at present but only one has been formally reported so far. This study suggested that marimastat had no survival advantage when compared to chemotherapy with gemcitabine in advanced pancreatic carcinoma. Current trials are assessing efficacy of MMPIs in maintenance of remission after other modalities of therapy or in combination with cytotoxic agents. MMPs have also been demonstrated to play an important role in the articular cartilage destruction seen in both rheumatoid arthritis and osteoarthritis. The use of MMPIs in both ex vivo and in vivo models have shown promising results and trials are in process to assess their potential role in the control of articular destruction. The true therapeutic role of MMPIs await the results of these randomized studies.","publication_date":"1999,,","publication_name":"Investigational New Drugs","grobid_abstract_attachment_id":"45954982"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Matrix metalloproteinase inhibitors: Applications in oncology","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [49251607]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = false; window.loswp.appleClientId = 'edu.academia.applesignon';</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":45954982,"attachmentType":"pdf"}"><img alt="First page of “Matrix metalloproteinase inhibitors: Applications in oncology”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/45954982/mini_magick20190210-6093-q90ms1.png?1549859270" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/assets/single_work_splash/adobe.icon-574afd46eb6b03a77a153a647fb47e30546f9215c0ee6a25df597a779717f9ef.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">Matrix metalloproteinase inhibitors: Applications in oncology</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="49251607" href="https://independent.academia.edu/DYip1"><img alt="Profile image of D. 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Yip</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">1999, Investigational New Drugs</p></div><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":45954982,"attachmentType":"pdf","workUrl":"https://www.academia.edu/25624655/Matrix_metalloproteinase_inhibitors_Applications_in_oncology"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":45954982,"attachmentType":"pdf","workUrl":"https://www.academia.edu/25624655/Matrix_metalloproteinase_inhibitors_Applications_in_oncology"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div></div><div data-auto_select="false" 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href="https://www.academia.edu/86044395/Matrix_metalloproteinase_and_its_drug_targets_therapy_in_solid_and_hematological_malignancies_An_overview"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="16235537" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/16235537/Matrix_Metalloproteinase_Inhibition_Attenuates_Human_Pancreatic_Cancer_Growthin_Vitroand_Decreases_Mortality_and_Tumorigenesisin_Vivo">Matrix Metalloproteinase Inhibition Attenuates Human Pancreatic Cancer Growthin Vitroand Decreases Mortality and Tumorigenesisin Vivo</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35330291" href="https://independent.academia.edu/AlexanderRosemurgy">Alexander Rosemurgy</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Surgical Research, 1997</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix Metalloproteinase Inhibition Attenuates Human Pancreatic Cancer Growthin Vitroand Decreases Mortality and Tumorigenesisin Vivo","attachmentId":42625998,"attachmentType":"pdf","work_url":"https://www.academia.edu/16235537/Matrix_Metalloproteinase_Inhibition_Attenuates_Human_Pancreatic_Cancer_Growthin_Vitroand_Decreases_Mortality_and_Tumorigenesisin_Vivo","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/16235537/Matrix_Metalloproteinase_Inhibition_Attenuates_Human_Pancreatic_Cancer_Growthin_Vitroand_Decreases_Mortality_and_Tumorigenesisin_Vivo"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="9380772" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/9380772/Is_there_new_hope_for_therapeutic_matrix_metalloproteinase_inhibition">Is there new hope for therapeutic matrix metalloproteinase inhibition?</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="9683486" href="https://ugent.academia.edu/RoosmarijnVandenbroucke">Roosmarijn Vandenbroucke</a></div><p class="ds-related-work--abstract ds2-5-body-sm">Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that form a family of 24 members in mammals. Evidence of the pathological roles of MMPs in various diseases, combined with their druggability, has made them attractive therapeutic targets. Initial drug discovery efforts focused on the roles of MMPs in cancer progression, and more than 50 MMP inhibitors have been investigated in clinical trials in various cancers. However, all of these trials failed. Reasons for failure include the lack of inhibitor specificity and insufficient knowledge about the complexity of the disease biology. MMPs are also known to be involved in several inflammatory processes, and there are new therapeutic opportunities for MMP inhibitors to treat such diseases. In this Review, we discuss the recent advances made in understanding the role of MMPs in inflammatory diseases and the therapeutic potential of MMP inhibition in those conditions.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Is there new hope for therapeutic matrix metalloproteinase inhibition?","attachmentId":35631485,"attachmentType":"pdf","work_url":"https://www.academia.edu/9380772/Is_there_new_hope_for_therapeutic_matrix_metalloproteinase_inhibition","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/9380772/Is_there_new_hope_for_therapeutic_matrix_metalloproteinase_inhibition"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="16235580" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/16235580/Addition_of_Matrix_Metalloproteinase_Inhibition_to_Conventional_Cytotoxic_Therapy_Reduces_Tumor_Implantation_and_Prolongs_Survival_in_a_Murine_Model_of_Human_Pancreatic_Cancer">Addition of Matrix Metalloproteinase Inhibition to Conventional Cytotoxic Therapy Reduces Tumor Implantation and Prolongs Survival in a Murine Model of Human Pancreatic Cancer</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35330291" href="https://independent.academia.edu/AlexanderRosemurgy">Alexander Rosemurgy</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2000</p><p class="ds-related-work--abstract ds2-5-body-sm">Matrix metalloproteinases (MMPs) participate in basement membrane degradation, a critical step in invasion of cancer cells. We have previously shown that MMP inhibition of pancreatic cancers improves survival and decreases MMP production in vivo. The purpose of this study was to determine whether BB-94 was better than cytotoxic therapy and would increase the efficacy of cytotoxic therapy (gemcitabine) in a</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Addition of Matrix Metalloproteinase Inhibition to Conventional Cytotoxic Therapy Reduces Tumor Implantation and Prolongs Survival in a Murine Model of Human Pancreatic Cancer","attachmentId":38905914,"attachmentType":"pdf","work_url":"https://www.academia.edu/16235580/Addition_of_Matrix_Metalloproteinase_Inhibition_to_Conventional_Cytotoxic_Therapy_Reduces_Tumor_Implantation_and_Prolongs_Survival_in_a_Murine_Model_of_Human_Pancreatic_Cancer","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/16235580/Addition_of_Matrix_Metalloproteinase_Inhibition_to_Conventional_Cytotoxic_Therapy_Reduces_Tumor_Implantation_and_Prolongs_Survival_in_a_Murine_Model_of_Human_Pancreatic_Cancer"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":45954982,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":45954982,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_45954982" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. 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J Morphol …, 2010</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix metalloproteinases involvement in pathologic conditions","attachmentId":69727232,"attachmentType":"pdf","work_url":"https://www.academia.edu/52480522/Matrix_metalloproteinases_involvement_in_pathologic_conditions","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/52480522/Matrix_metalloproteinases_involvement_in_pathologic_conditions"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div 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