• First-in-the-world discovery that a loss of the GATA4 gene is a common key reason for the development of liver cancer, the second leading cause of cancer deaths worldwide
  • 7 in 10 liver cancer patients worldwide exhibit GATA4 gene deletion; affects 1 in 2 liver cancer patients in Singapore
  • This discovery has major implications for developing new drugs through a new pathway in liver cancer

Singapore, 25 July 2017 – A clinician scientist-led research team from the National Cancer Centre Singapore (NCCS) and their US partner from the Cleveland Clinic is publishing a study on their important discovery that the GATA4 gene, which contributes to normal liver development, is commonly deleted in liver cancer.

The study (titled “GATA4 loss-of-function in liver cancer impedes precursor to hepatocyte transition”) is the first-in-the-world study to identify that GATA4 is a key gene that guards the liver against cancer. Loss of this gene in liver affects the normal liver development and exposes the liver to significant risk of cancer development. GATA4 is a necessary gene for normal liver development and growth. It was discovered that the loss of GATA4 results in abnormal cellular machinery and division, causing unstable cells with wide ranging negative effects.

Associate Professor Toh Han Chong, deputy director and senior consultant at National Cancer Centre Singapore, is leader and co-senior author of the study. A/Prof Toh said: “In the last many decades of liver cancer research, the molecular understanding of this disease has not led to many therapies which impact on patient survival. We hope that this new finding will light up a treatment path towards greater benefit and outcomes for liver cancer patients.”

Professor Yogen Saunthararajah, co-senior author of the study, staff clinician, and professor at Cleveland Clinic, USA, said: “Liver cancer, or hepatocellular carcinoma (HCC), is the world’s second leading cause of cancer death. For the past decade or so, there has only been one drug approved for the treatment of liver cancer, which is sorafenib. If we are to develop new and more effective treatments, a crucial first step is to understand how the instructions for liver assembly go wrong and make liver cancer instead.”

The team is the first group to report the major roles of GATA4 loss in liver cancer. In normal liver, GATA4 is essential in gathering and regulating different necessary factors to execute the correct liver development programme. Loss of GATA4 in liver will result in uncontrolled growth of liver cells, leading to diseases, such as fatty liver, obesity, and cancer development.

NCCS Research Fellow, Dr Timothy Shuen, is co-first author of the study. Dr Shuen explained: “Losing the GATA4 gene is like losing one of the main guardians of the liver. The liver can no longer be protected from stress and the normal liver machinery is damaged.”

A/Prof Toh has just recently been awarded the National Medical Research Council (NMRC) clinician scientist – individual research grant 2016 and the NMRC National Senior Clinician Scientist Award 2017. These grant and award provide funding and opportunity to dive much deeper into vital mouse-to-man studies on how GATA4 loss leads to such major instability to normal cells and its surrounding environment. The grant also supports the testing of novel new therapies to overcome this key genetic defect.

According to the Singapore Cancer Registry (2011-2015), liver cancer is the third most common cause of cancer deaths in men and fourth most common for women in Singapore.

The study will be published in the Journal of Clinical Investigation (JCI) on August 1st, 2017 (Singapore Time). 

About National Cancer Centre Singapore

National Cancer Centre Singapore (NCCS) provides a holistic and multi-disciplinary approach to cancer treatment and patient care. We treat majority of the public sector oncology cases, and they are benefiting from the sub-specialisation of our clinical oncologists. NCCS is also accredited by the US-based Joint Commission International for its quality patient care and safety. To deliver among the best in cancer treatment and care, our clinicians work closely with our scientists who conduct robust cutting-edge clinical and translational research programmes which are internationally recognised. NCCS strives to be a global leading cancer centre, and shares its expertise and knowledge by offering training to local and overseas medical professionals. www.nccs.com.sg

About Cleveland Clinic

Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. Among Cleveland Clinic’s 51,000 employees are more than 3,500 full-time salaried physicians and researchers and 14,000 nurses, representing 140 medical specialties and subspecialties. Cleveland Clinic’s health system includes a 165-acre main campus near downtown Cleveland, 10 regional hospitals, more than 150 northern Ohio outpatient locations – including 18 full-service family health centers and three health and wellness centers – and locations in Weston, Fla.; Las Vegas, Nev.; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2016, there were 7.1 million outpatient visits, 161,674 hospital admissions and 207,610 surgical cases throughout Cleveland Clinic’s health system. Patients came for treatment from every state and 180 countries. Visit us at clevelandclinic.org. Follow us at twitter.com/ClevelandClinic.

For more information, please contact:

National Cancer Centre Singapore
Rachel Tan
Manager, Corporate Communications
Tel: +65 6236 9535
Email: rachel.tan.c.h@nccs.com.sg