关键词：结肠癌;化疗药物;化疗;基因组织识别;转移;肿瘤;核醣核酸酸;治疗
摘 要：Colorectal cancer (CRC) represents a major health burden, and is the third leading cause of cancer deaths in the U.S. In the past decade, the median survival among patients with metastatic CRC has significantly improved, primarily due the development of active chemotherapeutic regimens that include biological agents. However, despite this success, patients soon run out of therapeutic options and receive salvage therapy that results in only a few weeks of disease stability. We have proposed to employ a team science, systems biology based approach to rapidly identify novel anti-cancer agents and individualize therapeutic strategies in preclinical CRC models. In this Year 1 Progress report, we will present the tasks and key accomplishments achieved within this period of time. In brief, we have completed in vitro testing on a large panel of CRC cell lines for six novel anti-cancer agents. We have completed baseline gene expression profiling of our CRC cell lines panel and patient-derived CRC tumor explant models by high-throughput RNA sequencing approach. We have initiated the in vivo cell line derived xenograft models to test the efficacy of these novel anti-cancer agents and in the process of determining the down stream effectors of these targets by immunoblotting assays. Our research findings for RNA-seq analaysis will be presented at the 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Dublin, Ireland (November 6-9, 2012). In summary, we have accomplished all the tasks that we proposed in year 1.