University of California San Francisco
Helen Diller Family Comprehensive Cancer Center

Insights into p53 Tumor-Suppressor Gene to Fuel Cancer Strategy

By Jennifer O'Brien, UCSF News Services | January 26, 2007

UCSF scientists are reporting key insights into the p53 tumor-suppressor gene that they say should help harness the gene to treat cancer.

The gene is disabled in most forms of the disease, and its loss is often associated with increased malignancy, resistance to treatment and decreased patient survival.

Scientists have long considered restoration of the p53 gene a possible therapeutic strategy. However, they have not known whether restoring the gene would lead to its activation or what impact, if any, such activation would have on established tumors -- until now.

In a unique model of p53 signaling, UCSF scientists restored the gene in the tumor cells of mice with established lymphoma. The initial results were dramatic.

"The tumors were completely dead within hours," says senior author Gerard I. Evan, PhD, the Gerson and Barbara Bass Bakar Distinguished Professor of Cancer Research at the UCSF Comprehensive Cancer Center. The animals also survived significantly longer than mice in which p53 had not been activated.

"These results demonstrate that signals exist in established lymphomas that can engage and trigger p53," he says. "All the machinery is there -- all the signals leading to p53 -- and all the machinery downstream of p53 that can destroy cancer cells is in place. The only thing missing is p53 itself. Restoring p53 in these tumor cells is like engaging the clutch in your car -- it reconnects the cancer-sensing 'engine' to the cell death 'transmission.'

"This result is very good news to the many of us who are thinking about trying to restore p53 function in established human cancers."

At the same time, he notes, the tumors eventually re-emerged in all of the mice. The team analyzed how this occurred, and identified tactics for optimizing the gene's therapeutic impact.

(Note that in November 2007 the UCSF Comprehensive Cancer Center was renamed the UCSF Helen Diller Family Comprehensive Cancer Center.)

Read more at Jennifer O'Brien, UCSF News Services