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Zeroing in on enzyme to battle cancer

  Saturday, 07 l 08 l 2010 Source:  The Straits Times   
By: Grace Chua

A*Star researcher first identified and now aims to stop PRL-3, which promotes cancer growth

FOR more than 10 years, a mild-mannered, bespectacled researcher in Singapore has been in hot pursuit of an enzyme involved in the rapid growth of deadly cancers.

enzyme to battle cancerDr Zeng Qi, from the Agency for Science, Technology and Research’s (A*Star) Institute of Molecular and Cell Biology (IMCB), first identified the enzyme PRL-3 in 1998, in cells that were “going crazy, zhang ya wu zhao (Chinese for ‘baring teeth and brandishing claws’)”.

As it turned out, PRL-3, which stands for “phosphatase of regenerating liver-3”, is key to metastasis, a process in which aggressive lung, pancreatic and other cancers grow very fast and spread to other parts of the body. And it is commonly overproduced in human cancers, making it an ideal target for cancer treatment.

Since then, Dr Zeng, 50, has made it her mission to explore the enzyme’s function and stop it in its tracks.

Last year, her team was awarded a $3 million flagship grant for its research to make human antibodies to combat the cancer-growth enzyme, conduct antibody safety tests in animals, and take the antibodies through to early clinical trials. The grant, from A*Star’s commercialisation arm Exploit Technologies, is meant to shepherd the work from laboratory to industry.

Last month, Dr Zeng’s team published a paper in the journal Cancer Cell, offering conclusive proof that a particular protein, PCBP1, suppresses the translation of the PRL-3 gene and thus cuts down the enzyme’s production.

The finding is a simple, small piece of work. But this is how Dr Zeng operates, by chipping away bit by bit at a large problem. As a young researcher at IMCB, she made a name for herself in 1991 by helping to breed the world’s first genetically engineered rats for human diabetes studies. Later, she switched to cancer research as it delivered faster results.

Breeding transgenic mice requires fertilising the eggs, waiting for the animals to be born, and studying them in detail, and can take years, Dr Zeng explained. In comparison, cancer experiments take a few weeks to a few months.

“We make cancer metastasise in mice and try to rescue them using different treatments,” she said, in a kind of “mouse clinic”.

Already, her research has identified specific antibodies that block PRL-3-associated cancers in mice, and it is now up to A*Star to get them into clinical use. The passion for research runs in Dr Zeng’s family: her husband Heng Wanjin, 50, whom she met at Xiamen University in China’s Fujian province, is deputy director of IMCB. The couple have worked in Singapore for 20 years, and been Singapore citizens for 18 of those years.

Their elder son, 21, who was born in the United States while the couple were in graduate school, is now studying at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Ohio.

She said: “He said to me, ‘Mummy, if your cancer drugs work, we should set up a charity for children’s leukaemia’.”

Dr Zeng, whose younger son is in Raffles Institution, said: “If you are doing some research, at the end of the day, you must feel that your research can help people. It’s not just to publish papers and get promotions.”

Discovering new cancer signposts

BESIDES Dr Zeng Qi’s paper on the PRL-3 enzyme, two other cancer-related projects out of the Agency for Science, Technology and Research were published recently in top journals.

The Institute of Molecular and Cell Biology’s Dr Vinay Tergaonkar and colleagues from Singapore and the US found that a protein called Rap1 is an important marker of breast cancer.

They also found that levels of Rap1 and where they are found could serve as markers of various diseases, and that Rap1 may be essential to keeping breast cancer cells alive, meaning it would make a good target for cancer treatment.

Their research was published online last month in Nature Cell Biology.

In a separate project, the Institute of Medical Biology’s Dr Francoise Thierry and colleagues from Singapore and China studied types of human papillomaviruses (HPV) associated with cervical cancer.

Cervical cancer is the fifth most deadly cancer in women worldwide, according to World Health Organisation statistics, and it affects about 16 out of every 100,000 women a year.

The scientists found that a protein called HPV16 E2 can be detected at a very early stage of HPV infection, which could lead to earlier treatment for HPV and cervical cancer.

Their research was published in the journal Cancer Research in June.

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