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<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.
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