Systematic analysis of RNA binding proteins in modulating drug response

RNA 结合蛋白调节药物反应的系统分析

• 批准号: 9258133
• 负责人: Daniel Issac Dominguez
• 金额: $ 5.71万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9258133
• 关键词: Address; Aftercare; Alternative Splicing; Antimitotic Agents; Antineoplastic Agents; Apoptotic; Automobile Driving; Biological Assay; Cancer Biology; Catalogs; Cell Survival; Cells; Chemicals; Chronic Myelomonocytic Leukemia; Data; Data Set; Development; Disease; Drug Combinations; Drug Targeting; Drug resistance; Dysmyelopoietic Syndromes; Encyclopedia of DNA Elements; Epidermal Growth Factor Receptor; Event; Exhibits; Gene Expression; Gene Proteins; Genes; Genetic Transcription; Malignant Neoplasms; Mediating; Monitor; Mutate; Mutation; Normal Cell; Paclitaxel; Pathway interactions; Pharmaceutical Preparations; Pharmacotherapy; Proteins; RNA Processing; RNA Splicing; RNA analysis; RNA-Binding Proteins; Regulator Genes; Research Proposals; Resistance; Role; SRSF2 gene; Signal Pathway; Testing; Transcript; Variant; base; cancer cell; cancer genome; cancer therapy; clinically relevant; drug sensitivity; experimental study; inhibitor/antagonist; insight; mRNA Decay; mTOR Signaling Pathway; neoplastic cell; novel; overexpression; protein E; response; small hairpin RNA; small molecule inhibitor; therapy resistant; transcriptome; transcriptome sequencing; transcriptomics; tumor; tumor progression; tumorigenesis

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.

项目总结/摘要 这项研究计划的重点是癌症治疗的一个主要障碍，即耐药性。许多 肿瘤对治疗没有反应或最终停止反应。耐药性阻碍了 癌症治疗的发展;即使是显示出初步疗效的新癌症疗法，当肿瘤 停止回应。肿瘤药物反应根据突变和转录水平的不同而变化很大。 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（RBP）已经成为推动癌症进展的关键因素。RBP活性通常 在癌症中由于RBP基因突变或RBP水平变化而改变。此外，癌细胞 与正常细胞相比表现出大量改变的转录谱。鉴于限制性商业惯例的重要作用， 在调节转录组方面，对癌症生物学的完整理解需要系统的 评估RBP在癌症中的作用。我提出系统的实验来询问有何不同 RBP影响癌细胞对常见癌症药物的反应方式。