Apoptosis gene suggests new target for chemotherapy

Yale scientists who identified a gene that enables cancer cells to evade one of the body’s mechanisms for weeding out mutations have refined their understanding of the gene and suggested potential new avenues for cancer treatment.

Their findings, published in a December cover story in the journal Nature, show that the gene, called survivin, is concentrated on the mitotic spindle, a cell component that is central to the process of cell division. “Survivin was absolutely undetectable in normal tissues, but we found it over-expressed in all the most common human cancers,” said Dario C. Altieri, M.D., associate professor of pathology and leader of the study. Survivin inhibits apoptosis, the programmed death of cells, thereby allowing mutated cells to survive.

Because it is present at mitosis, the gene may also be the link between two processes researchers have long believed were connected, apoptosis and cell cycle regulation. In normal tissue, survivin is expressed only during embryogenesis and fetal development, where it is believed to play a role in controlling apoptosis to maintain homeostasis and organ and tissue development.

In its recent findings the team built on its 1997 discovery and cloning of survivin. “We are providing some mechanistic implications for why cancer cells might have selected this particular gene for survival,” said Altieri, who collaborated on the project with Pier C. Marchisio, M.D., Ph.D., of the S. Raffaele Scientific Institute in Milan. The next step, Altieri said, is to identify survivin antagonists that would increase the effectiveness of chemotherapy by removing survivin’s protective function on the mitotic apparatus.