A nuclear protein called Twist may provide an effective approach for treating triple-negative breast cancer, according to a recent study published in Cancer Cell. Twist is an accelerant of the epithelial-mesenchymal transition (EMT) program in human cells, which is significant because TNBC has an activated EMT program. EMT provides tumor cells with stem cell-like characteristics, making them resistant to chemotherapy and increasing their chances for early metastasis.
Researchers found that Twist interacted with a key nuclear transcription regulator, BRD4. When many DNA viruses (such as papillomaviruses) enter into human “host” cells during infection, they hijack host cell machinery to replicate and synthesize their viral DNA and proteins. BRD4 is the virus's favored molecule and is often seized by DNA papillomaviruses for gene transcription during replication and growth.
The study showed that two BRD4 inhibitors, JQ1 and MS417, can specifically disrupt the interaction of Twist with BRD4, resulting in the suppression of triple-negative breast cancer cells.
"This finding has significant clinical ramification, because drugs that can target the Twist-BRD4 interaction provide a new hope for treating life-threatening triple-negative breast cancer," said lead researcher Peter Zhou, associate professor of molecular and cellular biochemistry at the University of Kentucky Markey Cancer Center.
—Information from a news release from the University of Kentucky
Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.
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