Scientists at A*STAR's Genome Institute of Singapore (GIS) have identified genes that could be potential targets for anticancer agents in the treatment of aggressive breast cancer. The findings were reported in a paper published in the July issue of PNAS.
Patients diagnosed with triple-negative breast cancer (TNBC) have three important proteins missing, which account for higher relapse rates following treatment and lower overall survival rates. There is currently no effective therapy for TNBC and efforts to improve clinical outcomes have been hindered by the lack of effective targeted therapies.
Scientists at A*STAR GIS have discovered that a protein tyrosine phosphatase, known as ubiquitin-associated and SH3 domain-containing B (UBASH3B), is overexpressed in one third of TNBC patients. This protein supports malignant growth, invasion, and metastasis, largely through modulating the epidermal growth factor receptor (EGFR). It has been found that UBASH3B is expressed in high levels in American and Asian patients, demonstrating that it is not specific to one ethnic group.
Lead author Dr Qiang Yu commented in a press release, "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."
According to Tan Tock Seng Hospital consultant surgeon Dr Tan Ern Yu, a collaborator and co-author of the study, while some patients may remain free of the disease, there are other TNBC patients who relapse after standard treatment; the ability to predict which patients are more susceptible to relapse is, therefore, crucial because these patients could benefit from more aggressive treatments. He pointed out that at the moment, doctors are unable to make such predictions reliably and further validation is needed to confirm whether UBASH3B can be developed into a means of identifying these high-risk patients as well as a new form of treatment.
Dr Dave Hoon, Director, Department Molecular Oncology at the John Wayne Cancer Institute, USA, and co-author said, "Recent large-scale genomic analysis of breast cancer show that TNBCs are highly heterogeneous and patients’ tumors can have different molecular profiles. 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."