Good News for Triple Negative Cancers
Over the past decade, increasing attention has been paid to so-called triple negative breast cancers--meaning, those cancers that are ER negative, PR negative, and her2 negative. Since there are treatments that are especially effective for cancers that are positive in each of those domains (hormonal treatments for the ER and PR ones, and herceptin and others for her2 positive tumors), it has been frustrating and frightening for women to not have access to any of those possibile treatments. Obviously, triple negative breast cancers have been around forever, but the designation is relatively new, and many women with this diagnosis are especially anxious about the future.
From last week's San Antonio Breast Cancer Sympoisum comes this report of HDAC inhibitation sensitizing triple negative cancer cells to make them even more sensitive to chemotherapies. Rather than trying to summarize the science, here is the beginning of a good summary from Cancer Network and then a link to read more:
SABCS: HDAC Inhibition Sensitizes TripleNegative Breast Cancer Cells to PARP Inhibition
By Dave Levitan | December 7, 2012
Combining histone deacetylase (HDAC) inhibitors with PARP inhibitors or has the potential to be an effective treatment for triplenegative breast cancer, according to preclinical research presented this week at the San Antonio Breast Cancer Symposium (SABCS). HDAC inhibition yields molecular changes that make the cancer cells more sensitive to other treatment.
"In simple terms, we are trying to cause a ‘BRCAness' so that you confer on triplenegative breast cancer cells the sensitivity to PARP inhibitors or platinum therapy seen when BRCA1 mutations are present," said Kapil N. Bhalla, MD, chief of personalized cancer medicine at the University of Kansas Cancer Center in Kansas City. Triplenegative breast cancer is not treatable with standard hormone therapies.
(MORE: SABCS: Cognitive Impairment in Breast Cancer Patients Begins Even Before Chemo)
Tumor cells often rely on intact DNA repair pathways, involving proteins including ATR, CHK1, and BRCA1. Those three proteins require heat shock protein 90 (HSP90) to function, and previous work has shown that HDAC inhibition can deactivate HSP90.
"The icing on the cake, so to speak, was that in addition to inhibiting the DNA damage response through depletion of DNA repair proteins, HDAC inhibitors induced DNA damage. By using HDAC inhibitors, we were targeting the cancer two ways at once," said Bhalla in a press release.