Children's Cancer Research Unit

Neuroblastoma Research Program

• Research Directions
• Group Leader Profile
• Grants
• Recent Publications

Research Directions

Neuroblastoma is a common childhood cancer and is responsible for 15% of all cancer-related deaths in children. In some patients, neuroblastoma can be successfully treated with surgery. Unfortunately, in half of the children with neuroblastoma, the tumour is very aggressive and has spread to other parts of the body even at diagnosis. Two out of 3 patients die from high-risk neuroblastoma. Currently, the team is focusing on studying "telomeres" in neuroblastoma. The research is a collaborative effort with the Children's Medical Research Institute's Cancer Research Unit. Telomeres are special structures that protect the DNA of a cell. As part of normal ageing, telomeres get shorter and shorter to a point when the cell eventually dies. In contrast, cancer cells can grow indefinitely by maintaining the length of telomeres and achieve immortality. Studying telomeres in neuroblastoma tumours with different behaviours will help us understand why some, but not all, of these tumours behave so aggressively. Based on this knowledge, better treatments can be designed to improve the cure rate.

Our laboratory is using neuroblastoma cells cultured in the laboratory as well as tumours collected from neuroblastoma patients to:

• Identify mechanisms used by these tumour cells to maintain telomere length
• Investigate whether these mechanisms affect patient's outcome and determine whether this can be used as a marker to choose the most appropriate treatment for future neuroblastoma patients
• Detect the genetic changes in relation to telomere maintenance mechanisms in neuroblastoma tumours

Group Leader Profile - Dr Loretta Lau

Loretta Lau is the leader of the Neuroblastoma Research Program, the newest research program started in 2008 at the Children's Cancer Research Unit. As a clinician-scientist, she is a Clinical Research Fellow of the Cancer Institute of NSW and within the hospital she holds a paediatric oncologist (specialist in childhood cancer) appointment. She is also a senior lecturer in the Discipline of Paediatrics and Child Health at the University of Sydney.

Dr Lau obtained her medical degree from the University of Sydney, followed by a Master of Medicine in Clinical Epidemiology. She did her training in paediatric oncology at The Children's Hospital at Westmead and is a Fellow of the Royal Australasian College of Physicians. Loretta then spent 6 years in Canada to pursue further clinical and research training in paediatric oncology at The Hospital for Sick Children in Toronto, during which she completed a PhD focusing on neuroblastoma research supported by the James Fund for Neuroblastoma Research project grant. While in Toronto, she was awarded a Clinical Research Fellowship by the National Cancer Institute of Canada, the Young Investigator Award by the American Society of Pediatric Hematology/Oncology, the Brigid G Leventhal Scholar Award in Cancer Research and, the Young Investigator Award by the American Association of Cancer Research. Dr Lau returned to Sydney in 2008 to take up the Clinical Research Fellowship awarded by the Cancer Institute of NSW and to establish the Neuroblastoma Research Program. Dr Lau is also a Young Investigator within the Neuroblastoma Committee of the Children's Oncology Group, the world's largest childhood cancer research collaborative group. Her aim is to pursue a career in neuroblastoma research and, as a clinician-scientist, to bridge the "gap" between scientific progress in the laboratory and better treatment at the bedside.

Grants

Cancer Institute of NSW Clinical Research Fellowship
2008 - 2010: $913,000

Recent Publications

Lau L, Tai D, Grant R, Baruchel S, Malkin D. Factors influencing survival in children with recurrent neuroblastoma. Journal of Pediatric Hematology/Oncology 2004, 26:227-232.

Lau L, Supko JG, Blaney S, Hershon L, Seibel N, Krailo M, Qu W, Jimeno J, Bernstein M, Baruchel S. A phase I and pharmacokinetic study of ecteinascidin-743 (Yondelis) in children with refractory solid tumors. A Children's Oncology Group study. Clinical Cancer Research 2005, 11 (2 Pt 1):672-677.

Lau L, Baruchel S: Can Canada sustain paediatric phase I trials? A national survey of cancer relapse in children. Canadian Journal of Clinical Pharmacology 2005, 12(3) e229-e239.

Lau L, Krafchik B, Trebo M, Weitzman S. Cutaneous Langerhans cell histiocytosis in children under one year. Pediatric Blood and Cancer 2006, 46(1):66-71.

Lau L, Hargrave D, Bartels U, Esquembre C, Bouffet E. Childhood brain tumor information on the internet in the Chinese language. Child's Nervous System 2006, 22(4):346-351.

Lau L, Hansford LM, Cheng LS, Hang M, Baruchel S, Kaplan DR, Irwin MS. Cyclooxygenase inhibitors modulate the p53/HDM2 pathway and enhance chemotherapy-induced apoptosis in neuroblastoma. Oncogene 2007, 26: 1920-1931.

Lau L, Stuurman K, Weitzman S. Skeletal Langerhan cell histiocytosis in children: Permanent consequences and health-related quality of life in long-term survivors. Pediatric Blood and Cancer 2008, 50(3): 607-612.

Lau LMS, Nugent JK, Zhao X, Irwin MS. HDM2 antagonist Nutlin-3 disrupts p73-HDM2 binding and enhances p73 function. Oncogene 2008, 27: 997-1003

Lau LMS, Wolter JK, Lau JT, Cheng LS, Smith KM, Hansford LM, Zhang L, Baruchel S, Robinson F, Irwin MS. Cyclooxygenase inhibitors differentially modulate p73 isoforms in neuroblastoma. Oncogene 2009, 28: 2024-2033.

Lau LMS and Irwin MS. Molecular Pathogenesis of Neuroblastomas. In: Mehta MP, Chang SM, Vogelbaum MA, Guha A, editors. Principles and Practices of Neuro-Oncology: A Multidisciplinary Approach. New York: Demos Medical Publishing. (in press)