Special Interview with Prof. Terence Kin Wah Lee from Hong Kong Polytechnic University

Hepatoma Research is pleased to present an exclusive interview with Prof. Terence Kin Wah Lee, an esteemed new member of our Editorial Board in 2024. In this interview, Prof. Lee emphasized several key advancements in liver cancer research. First, he highlighted the potential of gut microbiome-based biomarkers to improve immune checkpoint inhibitor (ICI) efficacy in hepatocellular carcinoma (HCC). His team is tackling treatment resistance by targeting cancer stemness pathways and investigating immune cell modulation within the tumor microenvironment. He underscored the need for personalized immunotherapy due to liver cancer's heterogeneity, aiming to increase the success rate of ICI treatments. Prof. Lee also discussed the importance of clinically validating basic research findings to enhance therapeutic relevance. Lastly, he advised young researchers to prioritize technical skills, stay current with new techniques, and collaborate across disciplines for impactful research.

Interviewee Introduction

Prof. Terence Kin Wah Lee currently serves as Vice President of Hong Kong Polytechnic University (Applied Biology and Chemical Technology), Deputy Director of the PolyU Centre for Life Sciences, and Principal Investigator at the State Key Laboratory of Chemical Biology and Drug Discovery. His primary research areas include hepatocellular carcinoma (HCC), cancer stem cells, gut microbiome, therapeutic resistance, and cancer immunology. Prof. Lee brings a wealth of expertise and insights to the liver cancer research community.

Interview Details

Q1. The role of the gut microbiome in the occurrence and treatment of liver cancer has garnered significant attention. What do you see as the most promising research directions in this field?

Terence Kin Wah Lee: Recent research has elucidated the role of gut microbiota in modulating the efficacy of various treatments, including targeted therapies and immune checkpoint inhibitors (ICIs), for patients with liver cancer. At present, there is a paucity of reliable biomarkers for predicting ICI efficacy. The development of biomarkers based on gut microbiota could serve as a personalized approach to enhance the success rate of ICI treatment in HCC patients. Therapeutic strategies such as prebiotics, probiotics, and fecal transplants, in combination with ICI treatment, offer potential novel approaches for liver cancer management. In future research, investigators are increasingly focusing on elucidating the role of gut microbiota-derived metabolites and their correlation with protein biomarkers in ICI sensitivity through multi-omics analysis. Furthermore, there is a growing emphasis on investigating how gut microbiota within tumors influence ICI response in liver cancer patients through the utilization of advanced spatial transcriptomics techniques.

Q2. What innovative strategies does your team have to address treatment resistance in liver cancer?

Terence Kin Wah Lee: For over a decade, our research team has focused on elucidating the role of plastic cell state on drug resistance in liver cancer. Our findings have led to the development of novel combination therapies that target cancer stemness-related pathways. Currently, we are employing single-cell RNA sequencing and spatial transcriptomic analysis to investigate the role of cancer stemness in drug resistance. Additionally, we are exploring not only the intrinsic signaling pathways associated with cancer stemness-driven drug resistance but also examining how drug resistance is mediated through the modulation of various immune cells within the tumor microenvironment. Our objective is to combine targeting cancer stemness pathways with ICI therapy to potentially enhance the survival outcomes for patients with liver cancer.

Q3. In your opinion, how can cancer immunology be applied to the precision treatment of liver cancer?

Terence Kin Wah Lee: A significant challenge in treating liver cancer patients is the intra-tumor and inter-tumor heterogeneity. As with targeted therapies, immune checkpoint inhibitor (ICI) treatment cannot be uniformly applied to all patients. The current ICI therapy success rate of approximately 20% is notably low, underscoring the necessity for developing various biomarkers to enable personalized precision medicine. Given that liver cancer is driven by distinct oncogenic pathways in different individuals, it is imperative to comprehend the immune landscape influenced by these pathways. This understanding will facilitate the development of tailored immunotherapies for each patient, potentially enhancing treatment efficacy and response rates.

Q4. How do you think we can better integrate basic research with clinical applications to enhance the treatment outcomes for liver cancer?

Terence Kin Wah Lee: In current liver cancer research, fundamental scientific investigations and clinical studies operate concurrently. For instance, researchers in basic science employ diverse cell-based and murine models to elucidate novel biomarkers and potential therapeutic targets for liver cancer. To establish clinical relevance, these findings necessitate validation through various clinical analyses. Even subsequent to initial validation, the generalizability of the data should be further corroborated across multiple clinical centers. To enhance clinical applicability, basic scientists frequently endeavor to incorporate clinical samples into their research, aiming to identify biomarkers and targets with greater relevance to patient care.

Q5. What advice do you have for young researchers entering the field of liver cancer?

Terence Kin Wah Lee: To excel in liver cancer research, emerging scientists should initially establish a robust knowledge base by staying current with the rapidly evolving techniques and knowledge in the field. Subsequently, they ought to identify research gaps within the field of liver cancer, concentrating on studies that could potentially enhance patient outcomes. Additionally, it is crucial to master cutting-edge technologies and methodologies, such as advanced imaging, mouse models, single-cell RNA sequencing, and spatial transcriptomics and proteomics. Recognizing the significance of collaborative research in today's scientific landscape, young researchers should seek partnerships with experts across various disciplines through interdisciplinary projects and conference attendance. Last but not least, they must maintain engagement with clinical perspectives by obtaining up-to-date information from healthcare professionals and diverse mentors.

Editor: Eric Zhang
Language Editor: Catherine Yang
Production Editor: Yan Zhang
Respectfully Submitted by the Editorial Office of Hepatoma Research