Editors' ChoiceHead and Neck Cancers

Weeding the Tares, Sparing the Wheat

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Science Translational Medicine  08 Jun 2011:
Vol. 3, Issue 86, pp. 86ec87
DOI: 10.1126/scitranslmed.3002721

Destroying malignant cells without hurting normal cells is similar to the fabled agricultural challenge of having both wheat and tares growing in the same field: Throughout much of the growing season, the tares look like wheat, making it difficult to distinguish the poisonous weed from the nutritious grain.

In the field of chemotherapy research, a promising strategy is to take advantage of features that subtly distinguish cancerous cells from normal cells; to this end, Bachar et al. report exciting progress. The authors prepared nanosized particle clusters composed of glycosaminoglycan, which they refer to as “gagomers,” and coated them with hyaluronan (HA). CD44 is a cell-surface glycoprotein receptor for HA that affects cell signaling, differentiation, proliferation, and migration. Using primary cells from head and neck cancerous tissue from five patients—with adjacent normal cells taken from each patient as a control—the authors observed CD44 on both normal and malignant cells. Despite this uniform expression, fluorescent HA-coated particles bound preferentially to the cancer cells. When the gagomers were loaded with mitomycin C—an anticancer drug that inhibits DNA synthesis but is generally toxic to humans—the particles showed selective cytotoxicity, affecting only the malignant cells. Normal cells maintained about 95% survival, but the survival rate of the cancerous cells was reduced to 10 to 20%. Bachar and colleagues speculated that the cancerous cells express different splice variants of CD44 on their surface, or that these cells have a mutant CD44 HA-binding domain, either of which causes the cells to have a higher affinity for HA than that of the wild-type binding domain.

Although mitomycin C is not currently used to treat head and neck cancers, a targeted drug delivery system such as these HA-coated gagomers might enable future treatments that will selectively weed out the destructive cells in patients, without destroying the surrounding healthy tissue.

G. Bachar et al., Hyaluronan-grafted particle clusters loaded with Mitomycin C as selective nanovectors for primary head and neck cancers. Biomaterials 32, 4840–4848 (2011). [Abstract]

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