Personalising Liver Cancer Treatment - NCCS Study Uncovers Possible Options
Thursday, 10 November 2005
FAQS
CURRENT SITUATION
Statistics
Globally 10.9 million new cases of cancer were diagnosed and approximately 6.7 million people died due to cancer in the year 2002(Global Action Against Cancer, WHO, UICC 2005).
Why focus on Liver cancer?
| 1. |
It is the sixth most common cancer worldwide- 626 000 new cases per year worldwide. |
| 2. |
Hepatocellular carcinoma (HCC) accounts for more than 90% of all primary liver cancers and represents approximately 40% of all cancer cases in South-east Asia. |
| 3. |
85-90% of HCC cases are inoperable. |
| 4. |
Patients with HCC experience a high mortality rate. Patients experience a high chance of relapse.
~ 95.5% of liver cancer patients die within 12 months
~ the median survival for inoperable HCC is 6 months.
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| 5. |
None of the non-surgical treatments has been conclusively proven to be effective in improving survival of both surgical and non-surgical patients. |
WHAT IS THE BREAKTHROUGH RESEARCH?
Aim
To search for treatment regimens that prolong survival of both surgical and non-surgical liver cancer patients.
Research project
A /Prof Huynh Hung uses xenografts to screen for appropriate targeted drugs and effective treatment. This involves implanting patients' cancerous liver cancer tissues into immuno-deficient mice. The mice bearing HCC xenografts were then given different types of chemotherapy and or small molecular targeted drug regimens to stop cell growth and promote apoptosis (cell death). The system efficiently identifies drugs that are more efficacious in treating tumours of individual patients. According to A/Prof Hung and his team, this study is one of the first in the world using actual tumours harvested from the patients to create human xenografts.
What's unique
| 1. |
The study involved a very close collaboration between clinicians and researchers to harvest the actual tumours. This classical translational research model is difficult to replicate where research laboratories and hospitals are located at a distance. |
| 2. |
In the past, researchers would grow xenografts from cell lines for their study. However this doesn't reflect the actual patient's tumour very well. Growing through many generations of culture changes them. Harvesting patients' actual tumour increases the chances of developing effective therapy that is appropriate for each patient. |
| 3. |
Xenograft banking of this kind is also useful to determine if future therapeutics are effective on the individual patient's tumour. |
| 4. |
If patients are not suitable for surgery, it is even more important for them to bank their tissues and have them tested against therapies. This is their only chance of being treated with appropriate therapies. For such patients biopsies are obtained to allow xenografts to be grown. |
| 5. |
There is a high accuracy in A/Prof Hung's track record of growing the xenografts and shrinking tumours in mice with the xenografts. |
| 6. |
A/Prof Hung's study is approximately one year away from implementation. Patients usually don't have the luxury of time on their side to benefit from research that takes too long to be translated from the bench to the bedside. |
FINDINGS
| 1. |
The screening system using xenografts from primary HCC obtained from patients works. |
| 2. |
Molecular targeted drugs blocking specific kinases (enzymes in the cell) and proteins have been shown to work well in HCC xenografts. |
| 3. |
Combining the above targeted drugs with conventional chemotherapy is more effective than monotherapy (use of just a single drug for treatment). |
Implications- Benefits
| 1. |
Discovery of system that potentially offers clinicians a better way to tailor HCC treatment in order to optimise benefit and minimize harmful side effects. |
| 2. |
The system takes away the guessing that is currently experienced by doctors who put patients on chemo drugs, then wait and see if the drugs work for the individual. |
| 3. |
The screening system shortens the time needed to identify the right drug that shrinks tumours. |
| 3. |
There is increasing accuracy of diagnosis using actual human tissues and not cell lines (cells with the ability to proliferate in animals) that have been artificially cultivated. This is because actual tissues harvested quickly and transplanted are not genetically defective. |
TEAM MEMBERS
| 1. |
A/Prof Huynh Hung, Principal Investigator, Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Centre, Singapore. |
| 2. |
Pierce KH Chow, Senior Consultant, Hepatobiliary and General Surgeon, Singapore General Hospital, Visiting Assoc. Professor, Nanyang Technological University, Visiting Surgical Oncologist, National Cancer Centre, Singapore, Director, Dept of Experimental Surgery, Singapore General Hospital. |
| 3. |
Prof Soo Khee Chee, Director, National Cancer Centre, Singapore. |
| 3. |
Ms Evelyn Tran, Research Officer, Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Centre, Singapore. |
BACKGROUND OF A/PROF HUYNH
Ph. D from McGill University, Montreal Canada - 1993
Project Director of Lady Davis Institute for Medical Research - 1994
Asst Prof, Department of Experimental Medicine, Mc Gill University - 1995
Principal Investigator, NCCS - 1999
Asst Prof, Department of Pharmacology, NUS - 2003
Numerous awards including:
Dean's First Honour List Award
Best Researcher Award SingHealth 2001
Best Grant Award
Canadian Cancer Research Society
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