Gene targets for triple negative breast cancers resistant to chemotherapy found

By Dr. Ananya Mandal, MDOct 4 2017

Researchers have finally found the genetic targets that could be used for treatment and development of new drugs in patients who are resistant to chemotherapy. These patients who are resistant to chemotherapy are most likely to have triple negative breast cancer which is the most aggressive form of breast cancer. The study appeared in the latest issue of the journal Cell Metabolism.

Researcher Dr. Carlos Arteaga, Director of the Harold C. Simmons Comprehensive Cancer Center and his colleagues have found that these chemotherapy resistant forms of breast cancers have increased activity of two genes, MCL1 and MYC. It is found that the activity of these two genes is responsible for development of chemotherapy resistance. This new study has shown that the increased activity of these two genes increase the mitochondrial oxidative phosphorylation. This action leads to the growth of chemotherapy-resistant cancer stem cells that makes the cancer resistant to chemotherapy and non responsive to treatment.

Dr. Arteaga, Professor of Internal Medicine at UT Southwestern Medical Center, explained that it is relatively easy to detect the alterations of these two genes using the tumor gene tests that are being used these days. Further this study could pave the way for development of drug targets that could inhibit MCL1 or MYC, or both. These drugs or their combinations can be tried in clinical trials to check if they can reduce the risk of development of chemotherapy resistance among patients with this most aggressive form of breast cancer he added. He said that the drugs that could inhibit MCL1 or MYC genes are already being developed. These drugs probably would be needed to be administered along with standard chemotherapies. He speculated that that these combinations would then slow or even prevent the onset or development of chemotherapy resistance. This would greatly benefit the thousands of women with this type of aggressive breast cancer.

The research took place at the Vanderbilt-Ingram Cancer Center. It received funding and support from Cure Foundation, the Breast Cancer Research Foundation, a National Institutes of Health Breast Cancer SPORE grant and Vanderbilt-Ingram Cancer Center Support Grant.

Triple negative breast cancer

Triple negative breast cancers are a type of breast cancer that does not display any estrogen receptors (ERs), progesterone receptors (PRs) or HER2 receptors. Breast cancers are usually described according to the presence or absence of these proteins (ER, PR or HER2). Those with none of these receptors are classed as having a triple negative cancer. These proteins present on the surface of cancer cells pick up messages which promote the cells' growth. The main importance of knowing if a cancer of the breast is triple negative is to determine the possible outcome of the cancer and its treatment options.

ER-positive cancers for example have cancer cells that may receive signals from estrogen that promote their growth. This is also referred to as an estrogen dependent cancer. A hormonal therapy that can decrease the amount of estrogen present in the body can therefore limit the growth of an ER-positive cancer. Women who have a triple negative cancer do not respond to hormonal therapy and are instead advised to undergo chemotherapy. Surgery is performed to remove the cancer after chemotherapy. Radiation therapy may also be beneficial in some cases.

In the United States, around 15 to 20 percent of all breast cancers are triple negative. Triple negative cancer is more common in women with certain characteristics including young age (less than 40 years), African American descent and those with Hispanic/Latina ethnicity. Women with BRCA1 mutations are more likely to get triple negative cancer.

Triple negative breast cancers are often very aggressive and tend to grow and spread quickly. They are also less likely to be detected on an annual mammogram and to spread to other parts of the body such as the brain, liver and bones. These cancers also tend to recur after treatment and remission meaning that overall, the prognosis for triple negative breast cancer is often poorer than with hormone positive cancers.