Washington,
Sep 8 - 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 ÒbrakesÓ 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.
ÒThis 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.
ÒThis 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,Ó
said Yu.
Added team member Prof Cheng Wee Joo: ÒThis
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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