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Discovery could enable targeted liver cancer therapy

Patients with hepatocellular carcinoma (HCC), the most common form of liver cancer, could have better chances of survival with the latest discovery by an international team of researchers.

The study led by Professor Daniel Tenen, Director of the Cancer Science Institute of Singapore (CSI Singapore) at NUS, was done jointly with the Brigham and Women's Hospital in Boston, the National University Health System, Queen Mary Hospital Hong Kong, Queen's University Belfast and Harvard Stem Cell Institute.

CSI Director Prof Tenen led the study on SALL4, a stem cell gene

The scientists found that SALL4 - a potent stem cell gene present in human foetuses for early development but inactive in healthy adult livers - can be used as a prognostic marker as well as a therapeutic target for HCC. They also proposed an approach that inactivates the gene to destroy HCC cells and prevent tumour formation.

The findings were published in the prestigious New England Journal of Medicine on 13 June 2013. Two patent applications have been filed on the breakthrough work.

Liver cancer is the third leading cause of cancer-related deaths in the world. According to the Singapore Cancer Registry, it is the fourth most common cancer in the country. The current diagnosis of HCC includes ultrasound, liver biopsy, computerised tomography, magnetic resonance imaging as well as blood tests to detect the presence of alpha-fetoprotein, a cancer marker.

In terms of treatment, surgical resection is the most viable treatment option for liver cancer, said Prof Tenen. However, this is only possible for early-stage liver tumours. "What urgently needs to be addressed is the development of more effective targeted therapies, and this is where our research comes in," he pointed out.

The investigators analysed 171 and 228 liver cancer samples from National University Hospital in Singapore and Queen Mary Hospital in Hong Kong respectively. They noted that 10 to 20 per cent of the liver cancer patients expressed high levels of SALL4, while 20 to 30 per cent expressed low to moderate levels of the gene. The expression of SALL4 is linked to a more aggressive subgroup of HCC, thus patients with higher expression should be considered for more aggressive treatment regimen where feasible as their condition will be more critical.

The researchers also determined SALL4's role in liver tumour formation. By suppressing the gene, the liver cancer cells can be killed or their tumour-forming capability blocked.

The findings may contribute towards targeted therapy for HCC. It could also help in the treatment of other types of cancers associated with SALL4 such as ovarian, endometrial, gastric, breast and lung cancers, as well as leukaemia.

PhD student and first author of the research paper, Ms Yong Kol Jia

National University of Singapore.

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