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NHMRC Early Career Fellowship (Australian Health Professional): The role Survivin and XIAP as biomarkers and therapeutic targets in paediatric acute myeloid leukaemia (2012–2016)

Abstract:
Conventional therapy for acute myeloid leukaemia (AML) is based on intensive use of cytarabine, etoposide and anthracyclines. For relapsed patients, most therapeutic regimens include further cytarabine in combination with other agents. Improvements in overall survival for childhood AML over the past 30 years can be largely attributed to more intensive use of conventional cytotoxics and improved supportive care. Chemotherapy with drugs such as etoposide and anthracyclines is limited not only by their acute toxicity, but also late effects such as an increased risk of secondary malignancy and cardiotoxicity. Such late effects are of particular concern in paediatrics since treatment occurs during periods of growth and development, and the duration of survivorship is much greater than adults. Less toxic and more effective therapies for AML in children, and adults, are therefore desperately needed. The human inhibitor of apoptosis protein (IAP) family consists of 8 proteins that perform multiple cellular functions. Survivin and X-linked IAP (XIAP) play key roles in regulating apoptosis, or programmed cell death. Survivin is also a key component of the chromosomal passenger complex, plays a nodal role in several networks of cellular division and death and appears to be important for normal haemopoiesis and leukaemogenesis. A number of small studies have reported Survivin and XIAP over-expression in AML with over-expression of each correlating with poor prognosis in some studies. Survivin and XIAP have emerged as attractive targets for cancer therapeutics. This project will determine the in vitro efficacy of a diverse range of conventional and selected novel therapeutic agents in a broad panel of paediatric and adult AML cell lines and primary samples. How efficacy relates to Survivin and XIAP expression and down-regulation will then be assessed. Finally, early-phase clinical trials of novel therapies targeting Survivin and XIAP will be developed for children with AML.
Grant type:
NHMRC Training (Postdoctoral) Fellowship
Researchers:

  • Dr Andy Moore

    ATH - Associate Professor
    Child Health Research Centre
    Faculty of Medicine
Funded by:
National Health and Medical Research Council