Research ArticleCancer

Mechanoresponsive stem cells to target cancer metastases through biophysical cues

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Science Translational Medicine  26 Jul 2017:
Vol. 9, Issue 400, eaan2966
DOI: 10.1126/scitranslmed.aan2966

A stiff punishment for tumors

In patients, tumor cells do not grow in isolation, and their behavior is regulated not only by their own biology but also by interactions with their microenvironment. A key part of the microenvironment is the extracellular matrix, which typically has a greater stiffness in tumors than in surrounding normal tissues. To take advantage of this, Liu et al. engineered mechanoresponsive mesenchymal stem cells to act as vehicles for cancer drug delivery. These engineered stem cells accumulated in tumors, delivering the first half of a two-part cancer therapy: the enzyme cytosine deaminase. A drug called 5-fluorocytosine was then delivered systemically, and cytosine deaminase in the tumors activated the drug, providing local anticancer activity with no off-target damage in mice.