Systematic analysis of RNA binding proteins in modulating drug response

项目摘要/摘要 这项研究建议重点关注癌症治疗中的一个主要障碍--耐药性。许多 肿瘤要么永远不起作用，要么最终停止对治疗的反应。抗药性阻碍了 癌症治疗的发展；即使是初见成效的新癌症疗法，当肿瘤出现时也常常失败 别再回应了。肿瘤药物的反应根据突变和转录水平的不同而显著不同 癌细胞的景观。一类与转录组相互作用并调节转录组的蛋白质，称为RNA 结合蛋白(RBPs)已成为推动癌症进展的关键因素。RBP活性通常是 在癌症中由于RBP基因突变或限制性商业惯例水平的变化而改变。此外，癌细胞 与正常细胞相比，表现出大量的转录变化。鉴于限制性商业惯例的重要作用 在调节转录组的过程中，对癌症生物学的完整理解需要一个系统的 限制性商业惯例在癌症中的作用评估。我提议进行系统的实验，以检验不同 限制性商业惯例影响癌细胞对常见抗癌药物的反应方式。

PROJECT SUMMARY/ABSTRACT This research proposal focuses on a major obstacle in the treatment of cancer, drug resistance. Many tumors either never respond or eventually stop responding to therapies. Drug resistance has stymied the development of cancer cures; even new cancer therapies that show initial efficacy frequently fail when tumors stop responding. Tumor drug response varies dramatically based on mutations and the transcriptional landscape of cancer cells. A class of proteins that interact with and regulate the transcriptome, termed RNA binding proteins (RBPs), have emerged as key players in driving cancer progression. RBP activity is commonly altered in cancer due to mutations in RBP genes or changes in the levels of RBPs. In addition, cancer cells exhibit massively altered transcriptional profiles as compared to normal cells. Given the important role of RBPs in regulating the transcriptome, a complete understanding of cancer biology demands a systematic assessment of the role of RBPs in cancer. I propose systematic experiments that interrogate how different RBPs influence the way a cancer cell responds to common cancer drugs.