The Key to Cannibalistic Cancer Cells

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A major problem in treating ovarian and breast cancers is the reawakening, sometimes years later, of dormant cancer cells that survive the initial treatment.

Doctors have long been puzzled by the phenomenon, reasoning that if any remaining cancer cells continued to grow normally, the disease would reappear in a matter of weeks or months.

But now researchers at The University of Texas M. D. Anderson Cancer Center, writing in the December issue of the Journal of Clinical Investigation, have reported discovering a single tumor-suppressing gene that is the key to understanding — and, they hope, eventually killing — dormant ovarian cancer cells.

A gene called ARHI acts as a kind of switch for autophagy, or self-cannibalization, in ovarian cancer cells; in this case, "self-eating" acts as a survival mechanism for dormant cancer cells, roughly comparable to a human's burning of body fat to survive without food.

"Prolonged autophagy is lethal to cancer cells, but a little autophagy can help dormant cancer cells survive, possibly by avoiding starvation," said senior author Robert Bast in a press release announcing the findings.

ARHI is short for "aplasia Ras homolog member I," a gene found in normal cells but underexpressed in about 60 to 70 percent of ovarian cancers. When ovarian cancer cells in the laboratory were dosed with normal levels of ARHI, autophagy was induced, killing the cancer cells within a few days.

The experiments then moved to human ovarian cancer grafts in mice, where the researchers observed a different effect. ARHI stopped tumor growth and induced autophagy, but left the cancer cells alive; when ARHI was turned off at four to six weeks, the ovarian cancer cells grew rapidly.

"When we blocked autophagy with chloroquine, a drug also used to treat malaria, regrowth of the cancers was inhibited, suggesting that autophagy had helped the cancer cells to survive in the absence of a blood supply," Bast said.

The discovery is especially important because it gives scientists a usable model for tumor dormancy; without it, scientists had been hindered in trying to develop treatments to eliminate the dormant cancers.

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