In the diagnosis of breast cancer is important to determine its subtype: HER2-positive or HER2-negative.
Scripps Research Laboratory describes the displacement of three different cancer cell lines of HER2-negative status in HER2-positive with the addition of selective molecules linking microRNAs, which the researchers call of TGP-515.
The idea is that the cancer genotype should not become a limiting factor in determining treatment options. However, this is only the first step in a long series of future work, which will allow new technology to benefit patients.
A team of researchers has developed a connection, using a mathematical Inforna system. Compound did cancer cells susceptible for Herceptin (trastuzumab), and for kadsily (adotrastuzumab emtanzin).
"It is possible that drugs such as Herceptin, may become available to a wider group of people by changing the expression of genes by means of therapeutic agents that bind to proteins are not, and with a non-coding RNA" - Matthew Disney says head of the laboratory.
About 20 percent of people diagnosed with breast cancer have HER2-positive mutation, which means that on the surface of cancer cells contain more protein HER2. Although this mutation is associated with faster growth and more aggressive cancer, she had a good opportunity to effectively treat since 1998. Since was introduced herceptin, 10-year survival for HER2-positive subtype increased to 84 percent.
"This study is proof strategy to create sensitivity to the drug - Disney says. - It also confirms that the gene transcription can be modulated by using low-molecular weight compounds designed to bind to the corresponding non-coding RNA. This means that it is not amenable to treatment of the disease will be cured. "
According to the first author Matthew J.. Kostalesa, graduate student Scripps Research, there are several problems that need to be overcome in order to create an effective connection.
The first compound has been associated with two different miRNAs, 885 and 515. Later, the researchers realized that the connection can be designed for a single miRNAs. In the end, they created a molecule that has been successfully selected only for microRNA 515. As a result, cells produced elevated levels of HER2, making them sensitive to the drugs.
"Synthetic, biochemical and cellular experiments lasted three years - says Kostales. - It took a great effort, but the work is not yet complete. " It is important to note that this is the first step towards the creation of drugs to increase the sensitivity to HER2. Successful tests in cultured cells should be accompanied by tests in mouse models of cancer, and this process will take several years.