Breakthrough in neuroblastoma and breast cancer research identifies new treatment targets
A team of researchers have discovered a completely new pathway in which a cell protein causes two common forms of cancer, neuroblastoma and breast cancer.
In neuroblastoma, the most common tumour of infants, and breast cancer, levels of the Myc proteins are commonly elevated in tumour cells. High levels of the protein are also associated with poor treatment outcomes. However, the way in which these proteins cause cancer has remained unknown.
For the first time, researchers at Children's Cancer Institute Australia for Medical Research (CCIA), and collaborators in Italy, describe how the Myc proteins lead to tumour formation.
"Our results show that Myc proteins cause cancer by switching off genes involved in cancer prevention, such as transglutaminase 2 (TG2)," says Professor Glenn Marshall, Head of CCIA's Molecular Carcinogenesis Program and Director of the Centre for Children's Cancer and Blood Disorders at Sydney Children's Hospital.
"In addition to this, we have also shown that when the neuroblastoma and breast cancer cells are treated with a new class of anti-cancer drugs called histone deacetylase inhibitors (HDACIs), they are able to turn the TG2 gene back on, which then inhibits tumour growth."
The results which will be published this week in the prestigious Proceedings of the National Academy of Science USA journal, describe in detail the complex interaction between the Myc protein, TG2 gene and HDACI drug within tumour cells.
"This work highlights the importance of HDACIs for the treatment of cancers caused by the high levels of Myc proteins," says Professor Marshall.
"More importantly, we identify TG2 as a potential drug development target for the treatment of these cancers.
"We believe that TG2 mimetics, combined with HDACIs in cancer therapy, will have potent anticancer effects in cells driven by Myc proteins."
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This work was supported by funding from the National Health and Medical Research Council, Cancer Council New South Wales, Cancer Institute New South Wales, United States National Cancer Institute, University of New South Wales, Italian Association for Research on Cancer, Italian Ministry of University and Research, University of Bologna, and Regional Program for Industrial Research-ITT Emilia Romagna Region, Italy.
Children's Cancer Institute Australia for Medical Research is affiliated with the University of NSW and Sydney Children's Hospital.
Note to editors
The following manuscript will be published in the November issue of Proceedings of the National Academy of Sciences USA:
Liu T, Tee AEL, Porro A, Smith SA, Dwarte T, Liu PY, Iraci N, Sekyere E, Haber M, Norris MD, Diolaiti D, Della Valle G, Perini G and Marshall GM (2007) "Activation of tissue transglutaminase trascription by histone deacetylase inhibition as a therapeutic approach for Myc oncogenesis".
About CCIA
Children's Cancer Institute Australia for Medical Research (CCIA) is the only independent medical research institute in Australia devoted to research into the causes, better treatment, prevention and cure of childhood cancer. The vision of the Institute is to save the lives of all children with cancer and to eliminate their suffering, and its mission involves achieving this through world-class research.
Founded in 1976 by a dedicated group of parents and doctors who wanted to do something more in the fight against childhood cancer, CCIA opened its first laboratory in 1984. The Institute now employs over 150 staff and students, including more than 100 scientists.
Research at CCIA comprises a multifaceted approach to improving the outcome of childhood cancer sufferers. Overall, the research program includes basic, preclinical and clinical studies aimed at defining and achieving improved treatment for children with cancer.
