Liver cancer ranks fifth in Hong Kong’s 2022 cancer statistics, according to the Cancer Online Resource Hub of the Government of the Hong Kong Special Administrative Region of the People’s Republic of China. It is challenging to cure, as many cases are diagnosed at middle to late stages, resulting in lower cure rates. Additionally, it is the third-leading cause of cancer deaths, with 1,412 fatalities in 2022, accounting for 9.6% of all cancer-related deaths. Compounding the issue is the liver’s detoxification function, which can diminish treatment effectiveness.

In response to these challenges, two experts from PolyU are dedicated to advancing research and developing innovative methods to combat cancer and improve patient outcomes. Professors Terence Lee Kin-wah and Zhao Yanxiang, both Associate Heads and Professors in the PolyU Department of Applied Biology and Chemical Technology, are leading groundbreaking research titled “Finding New Ways to Combat Drug Resistance in Cancers”, which is featured in Nature, a British weekly scientific journal publishing the finest peer-reviewed research that drives ground-breaking discovery.

Their work focuses on overcoming resistance to immunotherapy through strategies such as autophagy induction and gut microbiota interventions. By stimulating the immune system to generate precise, tumour-specific responses, they aim to enhance treatment efficacy. Given that each patient’s tumour is biologically unique, a personalised approach is essential. PolyU’s interdisciplinary excellence is driving these significant advances in cancer drug research.

Exploring how CDK6 contributes to liver cancer treatment resistance

When treating cancer, cancer cells often activate alternative signalling pathways to resist drugs, making cases like liver cancer particularly challenging. To investigate why some liver cancer cells develop resistance to Lenvatinib, a targeted treatment for advanced hepatocellular carcinoma (HCC), Professor Lee’s research team identified a protein called CDK6 as a crucial factor that helps cancer stem cells survive, complicating treatment efforts. To address this issue, the team tested drugs that either block or degrade CDK6, conducting experiments both in vitro and in mouse models resistant to Lenvatinib.

Prof. Terence Lee Kin-wah (left) and his team evaluated drugs that either inhibit or break CDK6, a protein that complicates treatment efforts.

Investigate how autophagy affects liver cancer treatment

Further to this effort, Professor Zhao has been exploring the role of autophagy, a vital cellular process through which cells degrade and recycle their components, particularly in response to stress or nutrient deprivation. The role of autophagy in cancer is complex, as both insufficient and excessive autophagy can be detrimental to cancer cells. To address this, Professor Zhao proposed potential therapeutic strategies that specifically target autophagy. Her research team is investigating the manipulation of autophagy as a promising approach for new cancer treatments, particularly to overcome drug resistance in specific tumour types, such as certain liver cancers, where autophagy tends to be low.

Prof. Zhao Yanxiang (centre) is investigating new cancer treatments to address drug resistance in specific tumour types.