Seeking Hope for Liver Cancer Patients Liver cancer is fatal. Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer, accounting for 70 to 80 per cent of cases, while intrahepatic cholangiocarcinoma (iCCA) is present in 20 to 30 per cent of cases. Professor Carmen Wong Chak-lui, in the Department of Pathology, School of Clinical Medicine, was recently awarded two major grants – the Distinguished Young Scholars Fund of the National Natural Science Foundation of China (NSFC) and the Research Fellow Scheme (RFS) grant from RGC – to support her studies on the biology of metabolic dysfunction-associated steatotic liver disease (MASLD)-HCC and a specific molecular subtype type of iCCA, respectively. ‘The incidence of steatotic liver cancer is increasing worldwide; 18 per cent of liver cancer patients in Mainland China have both Hepatitis B virus infection and steatotic liver disease,’ she said. ‘Recent studies suggest that steatotic liver cancer may exhibit a less favourable response to immunotherapy than viral liver cancer.’ The NSFC fund will support her research into how lipids affect the functionality of immune cells, which might potentially influence the immunotherapy response in MASLD-HCC. The study will enable the design of innovative and tailored therapeutic approaches for HCC patients with MASLD. ‘There are nearly 10 first-line treatments for HCC but only one for iCCA, and the effect is very marginal,’ she said. Isocitrate dehydrogenase (IDH) mutations occur in 13 to 15 per cent of iCCA. While an IDH inhibitor was recently approved as iCCA secondline treatment, it often leads to resistance in patients. The RGC-RFS will support her investigation into the metabolic adaptations of IDH-mutated ICC after treatment and the identification of new druggable vulnerabilities that can overcome this IDH inhibitor resistance. She will also study how the IDH inhibitor influences the tumour microenvironment. Professor Wong’s team aims to garner insights crucial for future clinical trials for MASLD-HCC and iCCA. Her research holds promise for broadening treatment options and increasing long-term patient survival rates. Professor Wong’s research is aided by technologies such as single-cell RNA sequencing, flow cytometry and imaging – something she is very familiar with in her role as Assistant Dean (Core Platforms & Advancement). ‘Our work would not be possible without the support of the Core Facilities, and we are excited to see members of our Faculty make good use of these powerful technologies,’ she said. A key mission for her grants is mentoring, which Professor Wong is also keen on. Her team members will receive training opportunities and support to advance their careers. ‘We want to ignite their enthusiasm for liver cancer research,’ she remarked. ‘I am very fortunate to receive recognition from the NSFC and RGC to pursue this important research, which aims to address the unmet clinical needs of liver cancer patients,’ said Professor Wong. ‘We aim to pave the way for precision treatment in liver cancer by developing innovative therapies for patients with hepatocellular carcinoma associated with fatty liver disease. Our research also explores the metabolic adaptability of intrahepatic cholangiocarcinoma post-treatment and seeks to identify vulnerabilities that can overcome resistance to IDH inhibitors. Our ultimate goal is to improve treatment outcomes for liver cancer.’ Professor Carmen Wong Chak-lui 9 HKUMed News Winter 2024
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