Biomedicine

Deadly Communication

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Science  23 Apr 2004:
Vol. 304, Issue 5670, pp. 491
DOI: 10.1126/science.304.5670.491b

Cisplatin is a platinum-based chemotherapeutic drug that has been used to treat cancer patients for 30 years. Remarkably potent against certain solid tumors, cisplatin played a major role in the recent recovery from testicular cancer of champion cyclist Lance Armstrong. Its antitumor activity has been attributed to its ability to form covalent adducts with DNA that disrupt transcription and replication in individual tumor cells.

Work by Jensen and Glazer reveals an additional explanation for cisplatin's antitumor efficacy—one that, surprisingly, involves cell-cell communication. Studying tumor cells cultured at different densities, they found that cisplatin produces a “death signal” that is transferred to neighboring cells through connecting channels called gap junctions. Although the molecular nature of the damage signal is still unclear, its generation appears to require the activity of DNA-dependent protein kinase, an enzyme already known to play a role in the DNA damage response. This discovery may help explain why tumors show variability in their response to cisplatin, and it suggests new strategies for sensitizing tumors that are resistant to the drug. — PAK

Proc. Natl. Acad. Sci. U.S.A. 101, 6134 (2004).

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