Blocking DNA: HDAC inhibitor targets triple negative breast cancer

May 21, 2012

The histone de-acetylase (HDAC) inhibitor panobinostat is able to target and destroy triple negative breast cancer, reveals a new study published in BioMed Central's open access journal Breast Cancer Research. Researchers from Tulane University Health Sciences Center have shown that panobinostat was able to destroy breast cancer cells and reduce tumor growth in mice.

Approximately 15% of breast cancers are found at diagnosis to be triple negative. These aggressive tumours are missing both the estrogen receptor and , which means that they do not respond to hormonal therapies such as antiestrogens or . They also test negative for the growth factor receptor HER2 and cannot be treated with monoclonal therapy such as Herceptin, so there is a desperate need for treatment options to complement surgery and chemotherapy.

Whether DNA is active or not in cells is tightly controlled. DNA in the nucleus is wound around histones and effectively shut down. When a gene is required the cell acetylates the histone, relaxing the tight control over DNA and allowing the cells machinery access to the gene, eventually leading to protein production.

HDACs have the opposite effect and reduce DNA activity. Aberrant HDACs are possibly responsible for the lack of production of normal cellular controls which allow the uncontrolled growth of cancer cells. The researchers from New Orleans hoped that by blocking HDACs they could restore normal cell function.

The HDAC inhibitor panobinostat was able to increase histone acetylation in triple negative cell lines. There was also a concurrent decrease in cell division and increase in apoptosis (). Additionally, a marked increase in the epithelial cell marker E-cadherin was observed, indicative of a less aggressive cell type.

Dr. Bridgette Collins-Burow, who led the study, described the results, "Panobinostat selectively targeted triple negative and decreased tumor growth in mice. It was also able to partially reverse the morphological changes in cells to a more epithelial type. These results show a potential therapeutic role for HDAC inhibitors, especially panobinostat, in targeting the aggressive triple negative breast cancer."

Explore further: Novel technique switches triple-negative breast cancer cells to hormone-receptor positive cells

More information: Targeting triple-negative breast cancer cells with the HDAC inhibitor Panobinostat, Chandra R Tate, Lyndsay V Rhodes, H Chris Segar, Jennifer L Driver, F Nell Pounder, Matthew E Burow and Bridgette M Collins-Burow, Breast Cancer Research (in press)

Related Stories

Recommended for you

Combination therapy can prevent cytostatic resistance

November 26, 2015

Researchers at Karolinska Institutet have found a new way of preventing resistance to cytostatics used in the treatment of cancers such as medulloblastoma, the most common form of malignant brain tumour in children. The promising ...

Forecasting the path of breast cancer in a patient

November 23, 2015

USC researchers have developed a mathematical model to forecast metastatic breast cancer survival rates using techniques usually reserved for weather prediction, financial forecasting and surfing the Web.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.