Researchers at A*STAR’s Singapore Bioimaging Consortium (SBIC) have identified two new possible drug targets for liver cancer treatment.
The research study provided insights into metabolic changes specific to liver cancer development. They found that a metabolic pathway for the production of an amino acid called proline, controlled by key genes that were essential for cell proliferation and tumour growth in a predominant form of liver cancer. The study was a collaboration between A*STAR’s SBIC and Institute of Medical Biology (IMB), the National Cancer Center Singapore (NCCS), and the Pharmaceuticals Division of Bayer.
The research team led by Prof. Han Weiping, Deputy Director of SBIC and Head of the Laboratory of Metabolic Medicine, aimed to identify targets for developing effective treatments for liver cancer, by characterising the metabolic shifts in this disease. Tapping on SBIC’s multi-disciplinary capabilities in metabolomics, metabolic imaging, and cancer metabolism, the researchers compared the metabolic enzyme expression profiles of different laboratory models with those from liver tissues of normal and regenerating liver models.
New findings could help stop liver cancer growing and spreading
Prof. Toh Han Chong, Deputy Medical Director (Strategic Partnerships) of NCCS and a co-author of the study said, “These findings create exciting new possibilities for designing treatments against energy pathways that keep liver cancer growing and spreading. This will be a new window to add to drugs that respectively activate an anti-cancer immune system, improve the blood vessel system surrounding cancer and that switch off cancer activating signals.”
These findings collectively suggest that the proline biosynthesis pathway may be a specific and effective target in the treatment of HCC – the predominant form of liver cancer, and the key genes in the pathway PYCR1 and ALDH18A1 may offer a novel therapeutic strategy for liver cancer. Moving forward, the team plans to conduct small molecule screening for drug target validation of PYCR1 and ALDH18A1.
Advances will help patients who fail to fully respond to currently-available drugs
Prof. Han said, “Findings from this study highlight the importance of advancing our understanding of cancer metabolism to identify the main drivers of cancer. By identifying novel factors that can be targeted, our study paves the way for new treatments that can help patients who fail to fully respond to currently-available drugs. As we pursue PYCR1 and ALDH18A1 as targets in liver cancer treatment, we will also test whether these enzymes are also valuable targets for other cancers.”
The Singapore Bioimaging Consortium (SBIC) under the Agency for Science, Technology and Research (A*STAR), is a leading international preclinical bioimaging platform. It has a multidisciplinary team of biologists, physiologists, chemists, physicists, engineers, computer scientists, and clinicians and investigates human diseases which are major public health issues using molecular physiology and advanced bioimaging tools, in a translational and pivotal mode with the medical community and industrial partners. SBIC currently operates five joint laboratories with industrial partners under the form of public-private partnerships.
