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

AURORA-A癌基因位于染色体20 q上，在结直肠癌和直肠癌中最常过度表达。它编码参与有丝分裂细胞分裂多个步骤的激酶，因此有助于维持染色体稳定性。最近的研究表明，Aurora-A蛋白也可能是人类癌症（包括结直肠癌）治疗反应的关键调节剂，但其潜在机制尚不清楚。这项研究的目的是阐明Aurora-A在结直肠和直肠肿瘤发生中的作用，以及对临床相关治疗的反应。特别是，基于我们在研究化疗耐药性和染色体不稳定性机制方面的长期专业知识，我们将研究不同水平的Aurora-A如何影响体外和体内结直肠癌和直肠癌的生长。我们的目标是确定结直肠癌和直肠癌中不同水平的Aurora-A如何调节对放疗和化疗敏感性的分子机制。最后，我们将通过分析原发性直肠癌样本中AURORA-A的表达和治疗反应，将我们的结果置于临床数据的背景下。

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.