EGF receptor, DNA methylation and platinum resistance in ovarian cancer

卵巢癌中的 EGF 受体、DNA 甲基化和铂耐药

• 批准号: 8721742
• 负责人: Sabrina Leigh Samudio-Ruiz
• 金额: $ 12.92万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-12 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8721742
• 关键词: Address; Animals; Basic Science; Biomedical Research; Cancer Center; Cancer Patient; Carboplatin; Center for Translational Science Activities; Cisplatin; Clinic; Clinical; Clinical Research; Clinical Sciences; Clinical Trials; Clinical effectiveness; DNA Methylation; Data; Development; Development Plans; Diagnosis; Disease regression; Dose; Drug Targeting; Drug resistance; Environment; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Epigenetic Process; Faculty; Funding; Future; Gene Expression; Gene Silencing; Gene Targeting; Genes; Goals; Gynecologic Oncology; Human; In Vitro; Incidence; Investigation; Knowledge; Lead; Link; Location; Maintenance; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of ovary; Mentors; Methylation; Methyltransferase; Modeling; Molecular Biology; NCI Center for Cancer Research; National Cancer Institute; New Mexico; Outcome; Outcome Study; Patients; Pharmaceutical Preparations; Platinum; Play; Postdoctoral Fellow; Publications; Publishing; Receptor Activation; Receptor Inhibition; Recruitment Activity; Relapse; Relative (related person); Research; Research Design; Research Infrastructure; Research Institute; Research Personnel; Research Project Grants; Research Proposals; Research Support; Resistance; Resistance development; Resource Sharing; Role; Sampling; Scientist; Signal Pathway; Signal Transduction; Techniques; Testing; Therapeutic; Tissue Sample; Training; Translational Research; United States National Institutes of Health; Universities; Woman; Work; analog; anticancer research; base; cancer cell; cancer therapy; career; career development; chemotherapeutic agent; clinical application; genome wide association study; human tissue; in vitro Model; in vivo; in vivo Model; information gathering; inhibitor/antagonist; interest; meetings; novel; partial response; prevent; professor; programs; research and development; research study; respiratory; response; small molecule; success; treatment center

DESCRIPTION (provided by applicant): The overall goal of this research proposal is to gain a deeper level of understanding of the signaling pathways and mechanisms that govern the development of platinum resistance in ovarian cancer. A deeper level of understanding for how platinum resistance develops is necessary in the field of ovarian cancer research as this is a common occurrence in patients with ovarian cancer and it prevents clinical effectiveness. To date, efforts at preventing the acquisition of platinum resistance have been limited due to lack of knowledge on the mechanism for how it develops; while efforts to reverse platinum resistance after it has already developed have only shown partial response rates. This research project is to serve as a 5 year career development plan for Dr. Samudio-Ruiz to transition from post doctoral fellow to research assistant professor with the long term goal of becoming tenure track faculty. Specific training in additional techniques related to molecular biology and epigenetics will prepare Dr. Samudio-Ruiz for a successful career in biomedical research with particular focus on cancer and epigenetics research. Additional training in clinical and translational research will allow Dr. Samudio-Ruiz to disseminate information gathered from basic biomedical research to clinical applications; thus, potentially advancing the efforts of ovarian cancer treatment in the clinic. This significantly coincides with the National Cancer Institute's goal of supporting research that could lead to the advancement of cancer treatment. The location for this work is the University of New Mexico (UNM) which is known for its commitment to cancer research, specifically women's cancer research, as a whole as it is the state's only National Cancer Institute-designated cancer center and the Official Cancer Center of the State of New Mexico. UNM offers a supportive environment where investigators can take advantage of several shared resources through the UNM Cancer Research and Treatment Center (CRTC) which Dr. Samudio-Ruiz will take full advantage of. The proposed research will evaluate epigenetic mechanisms, specifically DNA methylation, and its role in the development of platinum resistance in ovarian cancer. Particular focus will be paid to the Epidermal Growth Factor Receptor (EGFR) as Dr. Samudio-Ruiz recently found a link between EGFR and DNA methylation and that work was just accepted for publication. The overall research design is to generate an in vitro model of platinum resistance to evaluate changes in DNA methylation associated with the development of platinum resistance and determine if inhibition of the EGFR can prevent development of resistance. Data generated from the in vitro model will also be confirmed in human tissue samples both before and after the development of platinum resistance; thus setting up future experiments that can be taken to in vivo and eventually clinical models.

描述（由申请人提供）：本研究计划的总体目标是更深入地了解卵巢癌铂耐药发展的信号通路和机制。在卵巢癌研究领域，深入了解铂耐药是如何发展的是必要的，因为这是卵巢癌患者中常见的现象，它阻碍了临床疗效。迄今为止，在防止获得铂电阻的努力受到限制，由于缺乏