Gene Study May Help Fight Triple-Negative Breast Cancer

So Moshe cried out to Hashem, saying, “O Hashem, pray heal her!” Numbers 12:13 (The Israel Bible™)

All cancers are frightening and difficult to fight, but some are more aggressive and virulent than others. Fortunately, against a rapidly spreading type of malignancy called triple-negative breast cancer (TNBC), Hebrew University of Jerusalem researchers have succeeded in finding a gene that can affect the spread (metastasis) of this type of cancer, which has a particularly high mortality rate.

“The only treatment available today against this kind of cancer is is chemotherapy, which does not always help,” researcher Saleh Khawaled, one of the study’s main researchers, said. “We looked for a more biological way to fight it.”

Khawaled is a doctoral student in the lab of Prof. Rami Aqeilan at the Institute for Medical Research Israel-Canada (IMRIC) at the Hebrew University’s Faculty of Medicine. The study, which is being published in the prestigious journal Cancer Research of the American Association for Cancer, reveals an important role for the cancer-fighting gene WWOX in controlling the metastases of this most-violent type of breast cancer. Their team included researchers at the Lautenberg Center for Immunology and Cancer Research of the Hebrew University-Hadassah Medical School, Mokpo National University in the Republic of Korea and the Wexner Medical Center at Ohio State University.

Prof. Rami Aqeilan (right) with his doctoral student Saleh Khawaled. (Courtesy Hebrew University)

Breast cancer is one of the most common cancers and is the second- leading cause of cancer among women. It is known that the chances of recovery decrease significantly after the development of metastasis; the death rate after metastatic formation now stands at 90%). Among the different types of breast cancer are TMBC, which is considered to be particularly metastatic, causing a very high mortality rate among those who contract it. TMBC tends to be aggressive compared to other types of breast cancer mainly due to lack of treatment, the spread and recurrence of the disease and the fact that it can appear in younger ages.

The researchers focused on the study of genes that affect the process of metastasis. While most of the current studies look at how to attack the growth of breast cancer, it was decided to examine the metastases themselves from the beginning of their activity.

Looking at the WWOX cancer suppressor gene in controlling the development of metastasis in TNBC, the researchers found that this gene affects the expression and activity of the important protein in the development of cancer, c-Myc, an effect that is able to release the inhibitory activity of microRNA-146a that is known to reduce the cancerous potential of cancer cells.

That is, according to the researchers’ innovative approach, activity on the WWOX gene will be able to influence the mechanism of movement of the cancer cell in the body so that it is unable reach the primary growth of important organs in the human body.

Much of the work was carried out in laboratory mice. The experiments in mice showed that the return of the WWOX gene to the cells in which it was absent significantly delayed the production of metastasis and vice versa.

“WWOX is a recognized gene for medical researchers, but it was discovered not long ago, in the early 2000s,” explained Khawaled. “It is a significant gene that affects many factors in the development of cancer, so it is important to study it. Our work has shown that its importance derives from the fact that they affect not only the onset of the cancer process, but also subsequent stages. Beyond that, the only treatment available today against TNBC is through classical chemotherapy, which does not always help patients with this type of cancer.”

In the context of finding biological ways and since the use of biological drugs is gaining momentum over the years, the researchers suggest that the use of microRNA-146a can be used as an independent therapy or as a complementary treatment with the chemotherapy currently used. Further studies, the team said, will examine, among other things, whether injecting microRNA into existing tumors helps to limit their metastatic potential.



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