S'pore team finds new way to fight cancer

Scientists in Singapore claim they have found a new way to target telomerase, an enzyme that is linked to 95 per cent of all human cancers.

At embryo stage, all human cells have telomerase, which helps them to divide and reproduce - a process essential to the formation of organs.

After birth, however, most of the cells no longer have telomerase and will divide only a certain number of times. This is why people age and eventually die.

In healthy people, only stem cells have telomerase so these cells can continue to differentiate into different body parts such as skin and hair to replenish them.

In some people, however, the telomerase is reactivated in other cells. This causes those cells to start reproducing again, an abnormality which could eventually lead to cancer.

Scientists from the Agency for Science, Technology and Research's (A*Star) Institute of Molecular and Cell Biology (IMCB) have discovered that a protein in the telomerase called TERT is linked to the reactivation, and they also found out how to block it to potentially treat cancer.

While pharmaceutical firms have developed drugs to block telomerase in an attempt to treat cancer, they have been highly toxic and also cause stem cell loss in patients, so none has made it to market so far.

TERT was previously known to be involved in regulating the length of telomeres - caps at the ends of human chromosomes. These determine how many times cells can divide and reproduce.

But the IMCB scientists knew that TERT was also related to cancer, because in previous research, when other scientists removed TERT from both cancer and normal cells, the cells died quickly even though the telomere lengths were not affected.

When the IMCB team bred mice genetically engineered to develop lymphoma, a cancer affecting the immune system, with mice that had their TERT removed, the offspring developed lymphoma more slowly and also later in life without any effect on their telomere lengths.

When a modified version of TERT - stripped of its function on telomeres - was reintroduced into the offspring, the cancer became more aggressive. This proved that TERT has a second, cancer-boosting function independent of its role in telomeres.

The IMCB team said its work could lead to new, non-toxic cancer treatments that target TERT without affecting its normal role in regulating telomeres.

Principal investigators Vinay Tergaonkar and Ernesto Guccione said the team is working with A*Star's Experimental Therapeutics Centre to develop drugs to block TERT.

He added: "We have tested preclinical drug candidates... against clinical samples, and they have shown promising results in suppressing cancer progression."

zengkun@sph.com.sg

This article was first published on June 1, 2015.
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