For Immediate Release
May 13, 2005

Research Leads to Breast Cancer Advances

BUFFALO, NY – Recent news reports of a potential “pap smear” for breast cancer had its origins in research conducted by Nicoletta Sacchi, PhD, now a Professor of Cancer Genetics at Roswell Park Cancer Institute (RPCI). This work, describing a method to detect aberrantly methylated RAR ß2 gene in cells of breast cancer patients, was first published in Oncogene, 19:1556-1563, 2000, and was the first step in the creation of this novel test for early detection of breast cancer. The method was included in a U.S. Patent awarded in 2004 to the Johns Hopkins University, where Dr. Sacchi was a Visiting Professor.

“The application of our research knowledge to cancer care is gratifying,” noted Dr. Sacchi. “Rigorous dissemination of our research results along with collaboration with other scientists weave together disparate pieces of knowledge that reveal how cancer develops and progresses and is essential in our efforts to fight this disease.”

The RAR ß2 gene is a useful marker due to “epigenetic” modifications that leave the gene unchanged, but make it “silent.” One of these changes, called “methylation” can be detected in tissue and is the basis for this test under investigation.

Dr. Sacchi and her colleagues also found that cancer cells that contain the silent and methylated RAR ß2, cannot be growth-inhibited by retinoic acid, (a bioactive derivative of Vitamin A) and the cancer cells grow unchecked. In a follow-up study, Dr. Sacchi found that it is possible to “awaken” the silent RAR ß2 gene by removing the epigenetic changes and thus “re-sensitizing” the gene to retinoic acid and control tumor growth (Cancer Research, 62:2455-2461, 2002). This strategy might lead to a potential therapeutic method in the future

RAR ß2 is silent in association with epigenetic changes, including methylation, in the cells of almost all common tumor types including breast, prostate, lung, colon, kidney, head and neck, uterus and bladder.

“Ongoing clinical studies in the United States are investigating the multiple possibilities associated with testing for RAR ß2 silencing in tumors, and re-sensitizing cancer cells to the tumor suppressor activity of Vitamin A derivatives” continued Dr. Sacchi. “My next goal at Roswell Park is to understand how we can prevent RAR ß2 from becoming silent in cells. My laboratory is engaged in identifying the genetic and environmental factors that can often lead to the loss of RAR ß2 tumor suppressor activity.”

Roswell Park Cancer Institute, founded in 1898, is the nation’s first cancer research, treatment and education center and is the only National Cancer Institute- designated comprehensive cancer center in Upstate New York. RPCI is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers. For more information, visit RPCI’s website at www.roswellpark.org, call 1-877-ASK-RPCI or e-mail askrpci@roswellpark.org.

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