Cancer Cell Biology and Signaling Research Program

项目摘要/摘要 Markey癌症中心的癌细胞生物学和信号(CS)研究计划包括一个强大的 由一组有凝聚力和高度协作的调查人员执行的一系列主题驱动的项目。 首要目标是更好地了解癌症信号网络，以便识别新的靶点 可以被利用来创造新的治疗组合。为了实现这一目标，CS课程被划分为 分3个主题领域：1)异常增殖和生存网络，2)肿瘤进展的决定因素 肿瘤细胞与其微环境的相互作用。内部相互关联的副主题 每个目标都反映了研究项目的范围和跨领域专题的个人专长。 “细胞信号。”其中包括癌基因/抑癌基因和激酶/磷酸酶基因的调控。 网络(主题1)；细胞运动/上皮-间充质转化和癌症干细胞对 治疗耐药性(主题2)；检查细胞和基质对癌症发展的贡献 和进步(主题3)。CS计划的成员是定义癌症信号通路的专家 这是癌细胞存活、增殖、侵袭、转移和破译的基本机制。 肿瘤与调控肿瘤生长动力学的微观和宏观环境之间的关系 肿瘤进展。CS成员包括生存/凋亡信号响应领域的领导者 生长因子/细胞因子、黏附和失巢细胞，以及上皮-间充质过程中的专家 过渡、细胞运动和侵袭。该计划的26名成员代表加州大学的3所学院 肯塔基州和9个不同的部门，反映了不同的学科视角，提供了重要的新 对CS计划主题领域的洞察。CS计划每年与癌症相关的外部资金总额为 740万美元(每年直接成本510万美元，其中240万美元(48%)来自国家癌症研究所)。成员 2013至2017年间出版了231份出版物，其中90份(39%)是方案间出版物，55份(24%)是方案间出版物 方案内，134个(58%)是机构间的。由CS计划联合负责人Vivek博士领导 Rangnekar(研究细胞存活和凋亡的专家)和Rina Plattner(肿瘤侵袭的专家 和转移)，CS研究的重点是通过确定 驱动癌症发展和进展的信号通路中的新治疗靶点。在……里面 与基础研究和临床翻译的其他项目负责人和副主任合作， CS计划的研究已导致2项新的临床试验和8项新的专利。此外，使用 癌症教育和辅导副主任，CS项目的联合领导人已经制定了一个 健全的导师制度，确保初级教员的成功。通过带来广泛的专业知识和 方案优势，CS方案共同提供了一个丰富的环境，以促进多学科 合作，并建立了将CS科学转化为临床的富有成效的管道。

PROJECT SUMMARY/ABSTRACT The Markey Cancer Center's Cancer Cell Biology and Signaling (CS) Research Program includes a robust array of thematically driven projects performed by a cohesive and highly collaborative group of investigators. The overarching goal is to better understand cancer signaling networks in order to identify novel targets that can be exploited to create new therapeutic combinations. To achieve this objective, the CS program is divided into 3 thematic areas: 1) Aberrant proliferation and survival networks, 2) Determinants of tumor progression and metastasis, and 3) Interaction of tumor cells with their microenvironment. Inter-related subthemes within each goal reflect the scope of the research projects and individual expertise across the cross-cutting topic of “Cell Signaling.” These include regulation of oncogene/tumor suppressor and kinase/phosphatase gene networks (Theme 1); contribution of cell motility/ epithelial-mesenchymal transition and cancer stem cells to therapeutic resistance (Theme 2); and examination of cellular and matrix contributions to cancer development and progression (Theme 3). Members of the CS program are experts in defining cancer signaling pathways that underlie the mechanisms of cancer cell survival, proliferation, invasion, and metastasis, and deciphering the relationship between the tumor and the micro- and macro-environments that modulate the dynamics of tumor progression. CS members include leaders in the field of survival/apoptosis signaling in response to growth factors/cytokines, adhesion, and anoikis, as well as experts in the processes of epithelial-mesenchymal transition, cell motility, and invasion. The 26 members of the program represent 3 colleges at the University of Kentucky and 9 different departments, reflecting diverse disciplinary perspectives that provided significant new insights into CS program thematic areas. The CS program has a total annual external cancer-related funding of $7.4M ($5.1M annual direct costs, of which $2.4M (48%) is from the National Cancer Institute). Members published 231 publications between 2013 and 2017, of which 90 (39%) are inter-programmatic, 55 (24%) are intra-programmatic, and 134 (58%) are inter-institutional. Led by CS program Co-leaders, Drs. Vivek Rangnekar (an expert in studying cell survival and apoptosis) and Rina Plattner (an expert in tumor invasion and metastasis), CS research focuses on reducing the most serious cancer burdens in Kentucky by identifying novel therapeutic targets in signaling pathways that drive cancer development and progression. In collaboration with other program leaders and Associate Directors for Basic Research and Clinical Translation, research of the CS program has led to 2 new clinical trials and eight new patents. Additionally, working with the Associate Director for Cancer Education and Mentoring, the Co-leaders of the CS program have instituted a robust mentoring system to ensure the success of junior faculty. By bringing a wide array of expertise and programmatic strengths, the CS program collectively provides a rich environment to facilitate multidisciplinary collaboration and builds a productive pipeline for translation of CS science into the clinic.