Discovery of Root Cause of Triple-Negative Breast Cancer May Lead to New Therapies
TNBC comprises about 15-20 percent of all breast cancer diagnoses; disproportionately affects women of African and Hispanic descent.
Targeted therapies to treat triple negative breast cancer (TNBC), an aggressive, highly-metastatic disease that comprises about 20 percent of breast cancer incidences and which cannot be treated with conventional methods, may soon be realized, say researchers from the Icahn School of Medicine at Mount Sinai. Their study, titled "Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer," recently published in the journal Cancer Cell, demonstrated that a newly-developed small molecule treatment could disrupt the cellular process that causes tumors and the spread of TNBC, an inflammation-associated cancer.
The research team included scientists from Mount Sinai, the University of Kentucky, M.D. Anderson Cancer Center, and the Sun Yat-sen University Cancer Center and Soochow University in China; it was led by Ming-Ming Zhou, PhD, Professor and Chair of the Department of Structural and Chemical Biology at the Icahn School of Medicine at Mount Sinai.
"In this study, using a mouse model for human breast cancer, we showed that TNBC's characteristics -- rapid tumor growth and metastasis -- is heavily dependent upon and fueled by markedly evaluated transcriptional activation of pro-inflammatory cytokines and chemokines," said Dr. Zhou. "Using a small molecule to target that gene transcriptional machinery, we further uncovered and validated a drug target for potential new treatment of TNBC, which account for more than 170,000 new breast cancers annually and which disproportionately affects women of African and Hispanic descent. While much more research needs to be done, our findings are very promising and give us hope in the overall war against breast cancer."
TNBC comprises all forms of breast cancer that lack the expression of three key cell-surface receptors, i.e. estrogen receptors (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2/neu). Currently, available treatments for breast cancer target only these receptors, and thus are not applicable to TNBC patients. TNBC is highly aggressive, highly metastatic, and much more likely to recur than other subtypes of breast cancer. The current standard of care for TNBC is surgery with adjuvant chemotherapy and radiation therapy, which is toxic to living cells and ineffective once the tumor has spread.
Key facts about TNBC:
• TNBC comprises about 15 to 20 percent of breast cancer incidences
• In 2012, the most recent year for which data is available, about 170,000 new cases of TNBC were reported worldwide
• TNBC disproportionately affects women of African and Hispanic descent
• TNBC occurs more often in younger women and affects women as early as in their 20s
• About 80 percent of breast cancer in people with an inherited BRCA1 mutation – the gene which increases one's risk of developing breast and ovarian cancer – are found to have TNBC
About the Mount Sinai Health System
Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.
Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.