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A signal that the end is near

Yale Medicine Magazine, 2004 - Summer

Contents

A chemotherapeutic agent used against cancer for more than 30 years has a secondary effect of inducing “death signals” that kill neighboring cells, according to Yale scientists.

The agent, cisplatin, disrupts transcription and replication in tumor cells. It helped cyclist Lance Armstrong recover from testicular cancer and also works against lung, neck, cervical and ovarian cancers. In a study published in the Proceedings of the National Academy of Sciences in April, senior author Peter M. Glazer, M.D./Ph.D. ’87, HS ’91, professor and chair of the department of therapeutic radiology, reported that cells affected by cisplatin can produce a death signal that also kills neighboring cells. The phenomenon occurs only when there is a high density of cells that touch each other and communicate through channels called gap junctions. It also appears to require the activation of DNA-PK, an enzyme involved in DNA damage response.

“If we can understand this mechanism,” Glazer said, “it will help us to identify potential targets for manipulation.”