Novel Molecular Biomarkers and Therapeutics for Colorectal Cancer

项目总结/摘要 据估计，2017年有135，000例新发病例和50，000例死亡，结直肠癌（CRC）是第二大癌症。 是美国癌症死亡的主要原因。因此，需要新的方法来阐明 儿童权利委员会，以确定个人在高风险的CRC，制定新的和更有针对性的战略，以防止 CRC，并开发新的更好的治疗方法。案例胃肠道肿瘤专科项目 卓越研究（GI SPORE）进行综合的跨学科人类研究 特别是专注于开发新的生物标志物和针对结肠直肠和食管癌的靶向治疗， 恶性肿瘤。Markowitz博士（单位主任）是一位医学肿瘤学家和全国领先的科学家， CRC的研究，是案例GI孢子的PI。Stephen Fink博士（研究专家）是高级成员， 他是Markowitz研究小组的成员，也是Case GI SPORE的成员。这项建议是根据 芬克博士的几项重大发现是案件持续成功的关键 GI孢子，并概述了芬克博士将在实现该计划的未来研究的目标发挥积极作用。 博士Fink的研究与SPORE项目1特别相关，该项目的重点是预测，预后， 15-羟基前列腺素脱氢酶（15-PGDH）的治疗应用。此外，芬克博士 在领导生物标志物开发方面的专业知识使他最近发现了CEMIP/KIAA 1199， 生物标志物用于检测和预后，并作为潜在的治疗靶点。这些发现揭示了 Case GI SPORE中的新研究途径。目标：作为15-PGDH研究的关键研究者，Fink博士 i）确定低水平的15-PGDH表达是否将鉴定患有以下疾病的个体： ii）确定15-PGDH和/或其他前列腺素途径基因的变异是否鉴定 对阿司匹林化学预防有反应的个体和癌症;和iii）确定关键调节者和 结肠15-PGDH信号传导的效应子。此外，作为一个SPORE开发项目的负责人， 在CEMIP上，Fink博士将指导研究：i）开发CEMIP的早期翻译应用， CRC的检测和预后;和ii）测试抗CEMIP抗体是否可以阻断肿瘤的体内生长。 这些研究的成功将：i）帮助识别普通人群中患上糖尿病风险增加的个体 CRC（15-PGDH研究）; ii）提供CRC化学预防和早期检测的新策略（15-PGDH 和CEMIP研究）;和iii）提供用于疾病治疗的新的治疗途径（CEMIP研究）。的 研究专家奖将提供支持，使芬克博士开发新的方法和技术 以及帮助促进芬克博士的长期目标是一个团队科学家谁提供专家指导， 发现和开发胃肠道孢子和癌症病例中的生物标志物和治疗靶点 中心

PROJECT SUMMARY/ABSTRACT With an estimated 135,000 new cases and 50,000 deaths in 2017, colorectal cancer (CRC) is the second leading cause of cancer mortality in the United States. Thus, new approaches are needed to elucidate the biology of CRC, to identify individuals at high risk for CRC, to develop new and better targeted strategies for preventing CRC, and to develop new and better treatments. The Case gastrointestinal cancers Specialized Program of Research Excellence (GI SPORE) conducts an integrated spectrum of transdisciplinary human research particularly focusing on developing novel biomarkers and targeted therapies for colorectal and esophageal malignancies. Dr. Markowitz (Unit Director), a medical oncologist and a leading scientist nationally in translational research of CRC, is the PI of the Case GI SPORE. Dr. Stephen Fink (the Research Specialist) is a senior member of the Markowitz research group and an integral member of the Case GI SPORE. This proposal is based on the several high impact discoveries that Dr. Fink has made that have been key to the continued success of the Case GI SPORE, and outlines the active role Dr. Fink will play in achieving the goals of future studies in the program. Dr. Fink's studies are of particular relevance to SPORE Project 1, which centers on predictive, prognostic, and therapeutic applications of 15-Hydroxyprostaglandin dehydrogenase (15-PGDH). Additionally, Dr. Fink's expertise in leading up biomarker development has resulted in his recent discovery of CEMIP/KIAA1199 as a biomarker for detection and prognosis, and as a potential therapeutic target. These findings have opened up new research avenues within the Case GI SPORE. Goals: As a key Investigator in 15-PGDH studies, Dr. Fink will be directly involved in: i) Determining if low levels of 15-PGDH expression will identify individuals with increased CRC risk; ii) Determining if variation in 15-PGDH and/or other prostaglandin pathway genes identify individuals and cancers that will respond to aspirin chemoprevention; and iii) Identifying key regulators and effectors of colon 15-PGDH signaling. Furthermore, as the lead person directing a SPORE developmental project on CEMIP, Dr. Fink will direct research studies to: i) Develop translational applications of CEMIP for early detection and prognosis of CRC; and ii) Test if anti-CEMIP antibodies can block in vivo growth of tumors. Success of these studies will: i) help identify individuals in the general population who are at increased risk for CRC (15-PGDH studies); ii) provide new strategies for CRC chemoprevention and early detection (15-PGDH and CEMIP studies); and iii) provide a new therapeutic avenue for disease treatment (CEMIP studies). The Research Specialist award will provide support to enable Dr. Fink to develop new methodologies and techniques as well as help facilitate Dr. Fink's long-term goal of being a team scientist who provides expert guidance in discovery and development of biomarkers and therapeutic targets within the GI SPORE and the Case Cancer Center.