FEATURE A Target on Cancer’s Stubborn Roots Cancer stemness enables cancer cells to self-renew and reinitiate, and they are implicated in such things as drug resistance and metastasis. Yet they have proven difficult to eradicate. In hepatocellular cancer (HCC), the most common type of liver cancer, cancer cells exhibit this stemness state, leading to tumour relapse. The problem of HCC stemness has been a longstanding interest of Professor Stephanie Ma Kwai-yee of the School of Biomedical Sciences, who now leads a major crossdisciplinary and cross-institutional RGC Theme-based Research Scheme (TRS) project to understand the biology of tumour stemness and its relationship with drug response and tumour relapse. The work will lead towards finding new targets for treatment. ‘We want to know more about stemness and less differentiated states in cancer cells because we feel this is the root of the tumour. Once we know what controls or regulates that stemness state, then we can better define new therapies that can be used to target these cells, as well as combinations of drugs that are already approved,’ she said. Recent technological advances allow researchers to probe into cell activity and interactions more deeply. With CRISPR gene editing and their own platforms, the team will identify and characterise the genes and combinations of genes that are critical to HCC stemness. They will explore mouse and human datasets to identify in vivo features associated with cancer cell plasticity. With sequencing technologies, they will examine how different cells in tissue interact spatially and develop drug resistance. Finally, with chemical biological approaches, they will discover new therapeutic interventions against HCC stemness. ‘New technologies will help us unveil new dimensions in ways that were not possible five years ago,’ Professor Ma remarked. ‘But this is not just about the technologies. We need the expertise of all our co-principal investigators to be able to analyse and interpret the results. We have both experienced professors and young, active assistant professors and they are all contributing immensely.’ Scientists and clinicians in experimental cancer biology, hepatobiliary surgery, immunology, computational biology, bioinformatics, synthetic biology and chemical biology are all part of the team, and come from The Chinese University of Hong Kong, The Hong Kong Polytechnic University and The Hong Kong University of Science and Technology, as well as HKU. ‘There is plenty to bind the team together. Everyone will have incentives and new initiatives that spring up. Also, since this project is five years long, we will be ready to respond to new developments as they arise,’ she said. Professor Ma is also Assistant Dean (Innovation & Technology Transfer) in the Faculty and, although it is not directly tied to her TRS project, she hopes in future to take advantage of the opportunities and support abounding to translate research into applications. ‘I have been working on cancer cell plasticity for about 18 years. Other than publications and grants, I hope to apply what I have learned to the real world,’ she stated. ‘The main goal at this stage is to generate unique knowledge and platforms around cancer stemness and liver cancer, contributing to evidence-based applications that could improve diagnosis and treatment outcomes for HCC patients.’ Professor Stephanie Ma Kwai-yee 6
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