The role of the AURORA-A oncogene in tumorigenesis and in the therapy response in colorectal and rectal cancer

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The AURORA-A oncogene, located on chromosome 20q, is most frequently over-expressed in colorectal and rectal cancer. It encodes for a kinase involved in multiple steps of mitotic cell division and thus contributes to the maintenance of chromosomal stability. The most recent work has indicated that the Aurora-A protein might also be a key modulator of therapy response in human cancer, including colorectal cancer, but the underlying mechanisms are unclear. The goal of this research proposal is to elucidate the role of Aurora-A in colorectal and rectal tumorigenesis and in the response to clinically relevant therapeutic treatments. In particular, on the basis of our long-standing expertise in investigating the mechanisms of chemotherapy resistance and chromosomal instability, we will investigate how different levels of Aurora-A affect the growth of colorectal and rectal cancer in vitro and in vivo. We aim to define the molecular mechanisms of how different levels of Aurora-A in colorectal and rectal cancer modulate sensitivity toward radiotherapy and chemotherapy. Finally, we will place our results into a context of clinical data by analyzing AURORA-A expression and therapy response in primary rectal cancer samples.