HDAC inhibitor targets triple negative breast cancer
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 progesterone receptor, which means that they do not respond to hormonal therapies such as antiestrogens or aromatase inhibitors. 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 breast cancer cell lines. There was also a concurrent decrease in cell division and increase in apoptosis (programmed cell death). 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 breast cancer cells 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.”
Can breast cancer be found early?
Screening refers to tests and exams used to find a disease, like cancer, in people who do not have any symptoms. The goal of screening exams, such as mammograms, is to find cancers before they start to cause symptoms. Breast cancers that are found because they can be felt tend to be larger and are more likely to have already spread beyond the breast. In contrast, breast cancers found during screening exams are more likely to be small and still confined to the breast. The size of a breast cancer and how far it has spread are important factors in predicting the prognosis (outlook) for a woman with this disease.
Most doctors feel that early detection tests for breast cancer save many thousands of lives each year, and that many more lives could be saved if even more women and their health care providers took advantage of these tests. Following the American Cancer Society’s guidelines for the early detection of breast cancer improves the chances that breast cancer can be diagnosed at an early stage and treated successfully.
American Cancer Society recommendations for early breast cancer detection
Women age 40 and older should have a screening mammogram every year and should continue to do so for as long as they are in good health.
- Current evidence supporting mammograms is even stronger than in the past. In particular, recent evidence has confirmed that mammograms offer substantial benefit for women in their 40s. Women can feel confident about the benefits associated with regular mammograms for finding cancer early. However, mammograms also have limitations. A mammogram will miss some cancers, and it sometimes leads to follow up of findings that are not cancer, including biopsies.
- Women should be told about the benefits, limitations, and potential harms linked with regular screening. Mammograms can miss some cancers. But despite their limitations, they remain a very effective and valuable tool for decreasing suffering and death from breast cancer.
- Mammograms for older women should be based on the individual, her health, and other serious illnesses, such as congestive heart failure, end-stage renal disease, chronic obstructive pulmonary disease, and moderate-to-severe dementia. Age alone should not be the reason to stop having regular mammograms. As long as a woman is in good health and would be a candidate for treatment, she should continue to be screened with a mammogram.
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Notes to Editors
1. 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)
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2. Breast Cancer Research is an international, peer-reviewed online journal, publishing original research, reviews, commentaries and reports. Research articles of exceptional interest are published in all areas of biology and medicine relevant to breast cancer, including normal mammary gland biology, with special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition, the journal publishes clinical studies with a biological basis, including Phase I and Phase II trials.
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