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      Digesting a Path Forward: The Utility of Collagenase Tumor Treatment for Improved Drug Delivery

      1 , 1

      Molecular Pharmaceutics

      American Chemical Society (ACS)

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          Abstract

          <p class="first" id="P1">Collagen and hyaluronan are the most abundant components of the extracellular matrix (ECM) and their overexpression in tumors is linked to increased tumor growth and metastasis. These ECM components contribute to a protective tumor microenvironment by supporting a high interstitial fluid pressure and creating a tortuous setting for the convection and diffusion of chemotherapeutic small molecules, antibodies and nanoparticles in the tumor interstitial space. This review focuses on the research efforts to deplete extracellular collagen with collagenases to normalize the tumor microenvironment. Although collagen synthesis inhibitors are in clinical development, the use of collagenases is contentious and clinically untested in cancer patients. Pretreatment of murine tumors with collagenases increased drug uptake and diffusion two to ten-fold. This modest improvement resulted in decreased tumor growth but the benefits of collagenase treatment are confounded by risks of toxicity from collagen breakdown in healthy tissues. In this review, we evaluate the published <i>in vitro</i> and <i>in vivo</i> benefits and limitations of collagenase treatment to improve drug delivery. </p><p id="P2"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/0685ffef-4deb-48e3-88ae-d2be1ccdeebc/PubMedCentral/image/nihms-1045033-f0004.jpg"/> </div> </p>

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          Author and article information

          Journal
          Molecular Pharmaceutics
          Mol. Pharmaceutics
          American Chemical Society (ACS)
          1543-8384
          1543-8392
          May 03 2018
          June 04 2018
          May 16 2018
          June 04 2018
          : 15
          : 6
          : 2069-2083
          Affiliations
          [1 ]Pharmaceutical Sciences and Pharmacogenomics Graduate Program, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, United States
          Article
          10.1021/acs.molpharmaceut.8b00319
          6764447
          29767984
          © 2018

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