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Biological Chemistry

Cancer tissue stiffness helps target chemotherapy

Researchers engineer stem cells that convert a prodrug into an active drug when they encounter stiff, metastasizing tumor tissue

by Sarah Everts
July 31, 2017 | A version of this story appeared in Volume 95, Issue 31

An image of a cancer cell.
Credit: Sci. Transl. Med.
Metastasizing tumor cells (red) produce more collagen (blue), making them stiffer. A new strategy uses this change in rigidity to activate the anticancer drug 5-fluorouracil.

As tumors metastasize, cancer cells within often stiffen up their microenvironment by increasing the production and cross-linking of collagen. This rise in rigidity helps the metastatic cells migrate and invade other regions of the body. Given the dearth of remedies to combat metastatic cancer, researchers led by Weian Zhao of the University of California, Irvine, designed a therapy that targets this surge in stiffness. Previous research had shown that mesenchymal stem cells have a tendency to home in on metastasizing cancer cells. The team also knew that when these stem cells encounter stiff tissue, they differentiate into bone or muscle by activating the expression of certain genes. So Zhao’s team engineered the stem cells to additionally produce an enzyme called cytosine deaminase after they encounter stiff tissue. This enzyme converts the prodrug 5-fluorocytosine into the active anticancer drug 5-fluorouracil. The team showed that in mice, using a metastasizing cancer tissue’s stiffness as a way to activate 5-fluorouracil might be a promising new chemotherapy strategy (Sci. Transl. Med. 2017, DOI: 10.1126/scitranslmed.aan2966).


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