Mechanisms of uptake of 18F-FDG in an in vivo model of c-kit induced neoplasia [ 2006 - 2008 ]

Research Grant

Researchers: Prof Rodney Hicks (Principal investigator) ,  Donna Dorow ,  Dr Carleen Cullinane ,  Prof David Thomas ,  Prof Grant Mcarthur
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Brief description Recent advances in the field of tumour biology have created strong interest in development of molecularly targeted anti-tumour drugs. These targeted drugs are expected to yield higher therapeutic indices with fewer side effects than conventional cytotoxic treatments. However, due to the complicated nature of cellular processes affected by a given treatment, and the high cost of bringing new drugs to the clinic, it is important to define both mechanisms of action and in vivo functional effects of targeted therapies early in the drug development process. Gastrointestinal stromal tumour (GIST) is a prime example of a cancer for which a rationally designed drug has been successfully used. GISTs are often associated with activating mutations in c-kit, a gene encoding a cell surface protein. A new drug, Imatinib, inhibits the activity of mutated c-kit and blocks growth of many GISTs. However, over time many GISTs become resistant to Imatinib creating the need to develop additional treatments. Unfortunately, this has been hampered by lack of both a good model system for testing new drugs and robust diagnostic procedures for defining response to treatment. We have now developed a mouse model of GIST that grows and responds to treatment in a similar manner to human GIST. Furthermore, using imaging technology specifically designed for small animal studies, we can quickly monitor and evaluate changes in response during treatment. We propose to use the model system together with small animal imaging technology to define mechanisms by which GISTs respond or become resistant to Imatinib. This involves defining specific molecules within cells that change activity after Imatinib treatment as well as testing a series of gene mutations that may be involved in drug resistance. The results of the study will help to define new targets for GIST treatment as well as validate the imaging strategy that may have wide application to monitoring targeted anti-cancer therapies.

Funding Amount $AUD 438,520.54

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant