Scientists have identified genes that are potential targets for therapeutic drugs against aggressive breast cancer. Out of the 1.5 million women diagnosed with breast cancer in the world annually, nearly one in seven of these is classified as triple negative. Patients with triple-negative breast cancer (TNBC) have tumours that are missing three important proteins that are found in other types of breast cancer. The absence of these three proteins make TNBC patients succumb to a higher rate of relapse following treatment and have lower overall survival rates. There is currently no effective therapy for TNBC. Using integrated genomic approaches, researchers at ASTAR's Genome Institute of Singapore (GIS) led by Dr Qiang Yu, in collaboration with local and international institutions, set out to search for targets that can be affected by drugs. The scientists discovered that a protein tyrosine phosphatase, called UBASH3B, is overexpressed in one third of TNBC patients. UBASH3B controls the activity of an important breast cancer gene. The researchers found that deleting this gene expression markedly inhibits TNBC cell invasive growth and lung metastasis in a mouse model.
They also showed that patients with TNBC tumours that have high levels of UBASH3B tend to be more likely to have early recurrence and metastasis. "The identification of target genes is always the most crucial first step towards treating a disease. It is heartening to know that UBASH3B is an important element of the pro-invasive gene network and targeting UBASH3B not only inhibits TNBC invasive growth, but also significantly reduces metastasis," said lead author Dr Qiang Yu. "Recent large-scale genomic analysis of breast cancer show that triple negative breast cancer are highly heterogeneous and patients tumours can have different molecular profiles," said Dr Dave Hoon, Director, Department Molecular Oncology at the John Wayne Cancer Institute, US, and co-author of the study. "Unlike more common breast cancers that often express oestrogen, progesterone or HER2 can be targeted by specific agents such as hormone therapy or Herceptin. "TNBC is the most difficult breast cancer to treat. The finding can help us develop new approaches for targeted therapy for this highly aggressive breast cancer," Hoon said. The study was published in the journal Proceedings of the National Academy of Sciences (PNAS).