New research is shedding light on the treatment of triple-negative breast cancer, among the most difficult of all cancers to treat. The research focused on molecules called microRNA, which help regulate gene expression and the development of proteins. Scientists were especially interested in MicroRNA-96, a troublesome molecule linked by some studies to multiple types of cancers and other diseases.
The Scripps research used a compound called targaprimir-96 that targets microRNA-96 in breast cancer cells, triggering apoptosis, a process where defective or mutated cells shut themselves down. After a 21-day study on lab animals, researchers concluded that the compound reduced the production of microRNA-96, encouraging bad cells to kill themselves and slowing tumor growth. Normal cells were not harmed by the compound, the researchers said. "The study represents a clear breakthrough in precision medicine, as this molecule only kills the cancer cells that express the cancer-causing gene—not healthy cells," Scripps researcher Matthew Disney says in a statement.
The relevant forms of breast cancer
Most breast cancers are either estrogen-receptor-positive (ER-positive), progesterone-receptor-positive (PR-positive) or express the human epidermal growth factor receptor 2 gene (HER2-positive). ER-positive and PR-positive breast cancers, which account for about two-thirds of all breast malignancies, are often treated with hormone therapy, while the monoclonal antibody drug trastuzumab (Herceptin®) may be recommended to treat HER2-positive breast cancer. These treatments are often combined with other therapies, such as chemotherapy and/or breast cancer surgery.
Triple-negative breast cancer gets its name from the absence of the ER, PR and HER2 breast cancer markers. It is usually treated with a combination of chemotherapy, surgery and/or radiation therapy. But without those markers, oncologists don’t have a specific hormone or gene to target as part of a more precise treatment regimen, making the cancer type more challenging to treat. Triple-negative breast cancer is more common in women under 50 and in many women who inherited the BRCA1 gene mutation. It also is more prevalent among African-American women than white or Asian women.
"With triple-negative breast cancer, these are patients who are younger, they relapse earlier and, most importantly, we don’t currently have treatment options when the patients are metastatic," say Ricardo Alvarez, MD, MSc, Director of Cancer Research & Breast Medical Oncologist at our hospital near Atlanta. "We have learned it is not one type of disease. It is at least eight different diseases, and in some, you can have a very nice response. So there are multiple clinical trials now trying to identify what sub-types of triple-negative breast cancer will respond to certain drugs."
MicroRNA-96 is on the radar for disease researchers worldwide. Because it discourages apoptosis, it may allow bad cells, including cancer cells, to grow and multiply. Scientists in Japan are exploring the molecule's role in pancreatic cancer. Researchers in China have linked microRNA-96 to glioblastoma multiforme, a complex form of brain cancer. Scripps scientists hope their early research into microRNAs will lead to new cancer treatments and strategies to attack other diseases, as well. "In the future we hope to apply this strategy to target other disease-causing RNAs, which range from incurable cancers to important viral pathogens such as Zika and Ebola," Scripps research associate Sai Pradeep Velagapudi says in the statement.
