Scientists in Singapore claim to have uncovered a new method to target an enzyme that promotes the oestrogen receptor-negative breast cancer, a finding which may pave the way for an effective treatment for the disease.

A team from the Genome Institute of Singapore and the National University of Singapore says it has found the way to target the enzyme EZH2 which puts people at risk of developing the oestrogen receptor-negative breast cancer, one of the most aggressive forms of the disease unresponsive to treatment.

According to them, the discovery may soon pave the way to develop more effective treatment strategy for aggressive breast cancers associated with EZH2.

It has been known that EZH2 enzymatic activity promotes cancer by inactivating some important tumour suppressors, which function as “brakes” to stop tumour growth.

Over-expression of EZH2 is often linked to aggressive and rapid spread of breast cancers, the most common cancer in women all over the world.

Therefore, EZH2 is an ideal target for breast cancer treatment, says the team whose findings have been published in the ‘Molecular Cell’ journal.

The team, led by Dr Qiang Yu, discovered that besides inhibiting tumour suppressor genes through its enzyme activity, EZH2 is also able to promote cancer through the activation of specific genes involved in the cancer pathway, called NF-kB that is associated with the aggressive oestrogen receptor- negative breast cancer.

These genes include inflammatory cytokines such as IL6 and IL8 which have important roles in breast cancer progression and cancer stem cell self-renewal. In fact, the team discovered that the latter gene-activating function of EZH2 does not require its enzyme activity.

“This work suggests that EZH2 may confer its oncogenic role in cancer not just through its gene silencing function of the tumour suppressors but also through its gene activation function of NF-kB pathway.

“This new understanding on how EZH2 works as a cancer-causing gene in breast cancer has important therapeutic implication, the results suggest that small molecule drugs that block enzyme activity of EZH2 may not work for cancers caused by EZH2’s activation genes in NF-kB pathway,” said Yu.

Added team member Prof Cheng Wee Joo: “This work has important clinical implications. EZH2 is currently thought to cause cancer through its enzymatic activity; hence inhibitors being developed mostly target EZH2’s enzymatic activity.”

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