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Cancer
Why do some cancer patients fail to respond to treatment while others recover? The question is of intense interest in medicine and in recent years has seen breakthroughs.
"Growing evidence supports the notion that human cancers can be considered as a stem cell disease," said Professor G.S.W. Tsao of the Department of Anatomy. He is co-convenor of the Cancer research theme and also Director of the Centre for Cancer Research in the Li Ka Shing Faculty of Medicine.
Only a small number of cells are capable of initiating tumour growth. These cancer stem cells (CSCs) confer cancer-specific properties, such as uncontrolled growth and the ability to metastasise. But they can also self-renew and generate new lines, and they are difficult to control.
"CSCs are believed to be resistant to conventional chemotherapies, thus leading to disease relapse and failure of treatment," said Professor R.T.P. Poon of the Department of Surgery and also co-convenor of the Cancer theme.
HKU has an excellent track record in cancer stem cell research. Our researchers have identified a cancer stem cell marker for hepatocellular cancer (in the liver), isolated cancer stem cells for colorectal cancer and studied the genetic basis of the disease, and identified an enzyme that is expressed in patients suffering from an aggressive form of leukaemia.
They have also developed new tracking and imaging methods for CSCs and uncovered important insights on cancer cell biology.
These are important steps forward but many questions still remain. Scholars from the Medical, Science and Engineering Faculties have proposed new research projects that they hope will ultimately lead to the development of novel and effective treatments for sufferers of these diseases.
Hepatocellular cancer
Hepatocellular cancer is primary cancer of the liver — it starts there, rather than spreading, or metastasising, from another location. It is the fifth most common cancer worldwide and particularly prevalent in Hong Kong and China. Researchers at the University are working to isolate CSCs at different stages of the cancer, as well as CSCs with metastatic properties, to shed light on their development and behaviour. The expectation is that this information will lead to more effective treatment.
Thus far, researchers of the Li Ka Shing Faculty of Medicine have successfully isolated CSCs from patients’ peripheral blood and are studying the prognostic implication of circulating CSCs.
Additionally, they are looking at how to treat liver cancer stem cells, first by validating the known CSC markers and defining their resistance to chemotherapy. Once that is done, the researchers will evaluate the use of Chinese herbal medicine, natural compounds, metal-based drugs and novel molecular targeting drugs to target liver CSCs.
Colorectal cancer
The second most common cancer in Hong Kong offers an interesting case study in cancer stem cells. Cancer needs blood vessels for nutrients and growth and colorectal CSCs are believed to send signals that recruit bone marrow-derived cells to help in this process. When the recruited cells arrive, they help to generate new blood vessels. Taking that as a starting point, HKU researchers will investigate the ability of colorectal CSCs to recruit cells, form blood vessels and send signals that help to initiate tumour growth. The results should contribute to global understanding about normal and tumour-causing cells.
HKU researchers have also successfully isolated a specific subset of CSCs capable of initiating metastasis from human colorectal cancer specimens. Further studies to characterise these will provide new insight into the biology of how cancer spreads and help to develop new strategies in inhibiting the spread of colorectal cancer.
Leukaemia
Adult myeloid leukaemia is a virulent disease with a high remission rate. Our researchers noticed in previous studies that leukaemia patients express a high level of the enzyme aldehyde dehydrogenase. In fact, there seems to be a co-relation between the enzyme and the aggressiveness of the disease.
Current research hopes to explain why this is happening. Cells that express high levels of aldehyde dehydrogenase will be isolated and studied to determine which genes are important in the disease-related role of the enzyme. This should facilitate better understanding of leukaemia stem cells and possible treatments.
Basic research on cancer stem cells
In addition to looking at the role of disease-specific cancer stem cells, we are also interested in a broader understanding of cancer cell biology. The factors and signalling pathways of CSCs are currently poorly defined. Upcoming research will look at the "stem" properties in CSCs and what regulates their renewal and development. The aim is to identify new targets for therapy, as well as markers for the disease that can be evaluated using clinical specimens.
