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Yi Li, PhD
Baylor College of Medicine
Goal: To test a novel chemopreventive agent as a potential alternative to hormone-based preventive drugs
Impact: Anti-estrogens are the only approved drugs for chemoprevention. While they are quite effective at reducing the risk of breast cancer, they also have side effects that some women can’t tolerate. Dr. Li’s BCRF project will test an alternative to hormone-based chemoprevention that could be more acceptable to women who are at increased risk of breast cancer.
What’s next: Dr. Li and his colleagues will test a targeted drug that causes cells to die in laboratory models to see if it can effectively prevent progression of benign tissue to cancer, thereby preventing aggressive forms of cancer.
Anti-estrogens, such as tamoxifen and aromatase inhibitors (AI) are effective at reducing the risk of estrogen receptor (ER)-positive breast cancer—the most common form of the disease. But in order to receive the full benefits, women have to take them for a minimum of five years. Many women do not complete the full regimen, however, due to side effects. Li and his colleagues are investigating if cell survival signals in pre-malignant cells can be targeted to prevent progression to cancer. This preliminary study will pave the way for additional research that could lead to an alternative to hormone-based chemoprevention.
Full Research Summary
Research area: To develop alternative strategies for chemoprevention.
Impact: Most breast cancers require estrogen to grow and the most effective prevention for this kind of breast cancer is anti-estrogen therapy. Long-term use of anti-estrogens, such as tamoxifen, are FDA-approved as chemoprevention. However, many women cannot tolerate the drugs because of their side effects. In addition, they are not effective in preventing breast cancers that do not require estrogen to grow, such as triple-negative breast cancer. Dr. Li is testing a drug called navitoclax that targets cell survival signals as a potential alternative to hormonal drug for breast cancer prevention.
Current investigation: BCL2 proteins are a group of proteins involved in normal cell growth. Cancer cells and precancerous cells may activate more of the BCL2 proteins to give them a survival advantage, thereby allowing cancer cells to grow uncontrollably and for the cancer to progress. Dr. Li and his team will be testing if the drug navitoclax, which targets BCL2, restores a cell-death program, killing precancerous cells. His research can lead to new preventive alternatives for women at high risk for breast cancer.
Dr. Yi Li is a professor at the Lester & Sue Smith Breast Center and the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
His team investigates the molecular and cellular mechanisms of breast cancer initiation and progression. Dr. Li’s lab has made a number of significant contributions to the field of breast cancer: his lab pioneered an intraductal laboratory model that closely recapitulates human breast tumorigenesis; discovered a molecular mechanism underlying the dichotomous effects of pregnancy on breast tumorigenesis; and established intermittent anti-STAT5 treatment for preventing breast cancer in preclinical models, which has resulted in a multicenter window-of-opportunity clinical trial (TBCRC042).