Susan G. Komen for the Cure™ has awarded a three-year, $600,000 grant to City of Hope to support research in reducing side effects and preventing drug resistance during treatment of hormone-dependent breast cancer.
City of Hope researchers are studying the combination therapy of aromatase inhibitors, which block the production of estrogen, and an investigational drug that specifically targets breast cancer cells.
A major focus of breast cancer research conducted at City of Hope centers on the role of aromatase, an enzyme that converts the male hormone androgen into estrogen. Shiuan Chen, Ph.D., the study’s principal investigator and co-leader of the Breast Cancer Research Program, studies the regulatory mechanism of aromatase expression in breast cancer cells. His lab was one of three internationally to discover that breast cancer cells produce their own estrogen.
|Shiuan Chen (Photo by Markie Ramirez)|
About 70 percent of breast cancers are hormone-dependent, requiring estrogen to survive and grow. Hormone-dependent breast cancers can be treated with drugs that block or control estrogen levels. “Aromatase inhibitors are a type of breast cancer drug that work by drastically lowering estrogen levels in the body,” said Chen, director of the Division of Tumor Cell Biology, Beckman Research Institute.
Aromatase inhibitors are effective in eradicating cancer, particularly in postmenopausal women, yet they produce debilitating side effects — from severe joint pain to bone loss and fractures. Another drawback is that patients who receive long-term treatment with aromatase inhibitors can become resistant to them.
Chen’s previous research concluded that an investigational drug, LBH589, is a potent inhibitor of aromatase expression in breast cancer cells, but does not affect healthy cells. The researchers believe that combining LBH589 with aromatase inhibitors such as letrozole may help prevent the side effects and drug resistance in the treatment of hormone-dependent breast cancer in post-menopausal women, because women will be able to take lower doses of the aromatase inhibitors.
“The Susan G. Komen for the Cure grant will help us understand how LBH589 works and explore whether a combination of typical aromatase inhibitors with this drug will produce a synergistic effect,” said Chen.
As what is called a histone deacetylase inhibitor, the drug may work through epigenetics — by silencing certain genes — and Chen wants to identify those silencing switches. Laboratory studies on the combination therapy also aim to understand the effectiveness of combination therapy in stopping estrogen production in breast cancer cells and in delaying resistance.
LBH589 already has been approved by the Food and Drug Administration for use in leukemia patients. If it proves effective during the current preclinical trials, its approval for leukemia means it eventually could be adapted and approved more quickly for use in breast cancer patients.
About 182,460 women in the United States will be diagnosed with breast cancer this year, according to the American Cancer Society.
Susan G. Komen for the Cure is the world’s largest grassroots network of breast cancer survivors and activists fighting to save lives, empower people, ensure quality care for all and energize science to find the cures. Since its inception in 1982, it has awarded more than 1,100 breast cancer research grants totaling more than $400 million; only the top 10 percent of applications to the highly competitive grant program are funded.