Research Program - Molecular Oncology

摘要 乔治城隆巴迪综合癌症中心（LCCC）分子肿瘤学项目（MO） 汇集了研究人员，他们的使命是识别和验证对人类免疫系统至关重要的分子途径。 癌症的发生、发展、维持和转移。MO的总体目标是了解 并为癌症易感性、起始和进展的复杂过程开发生物标志物， 鉴定新的靶点以及新的和重新利用的抗癌剂， 对正常细胞的毒性。为了完成这一使命和目标，MO成员在以下条件下进行研究： 两个目标：1）定义和利用启动和维持癌症的独特基因组和表观基因组事件 生长和2）确定干细胞样表型的生物学机制，改变 代谢和癌细胞的转移扩散。A.反映目标1进展的重大进展 Yi发现雅普调节胰腺导管腺癌的免疫抑制环境 （PDAC）。对于目标2，Chung发现茶酚酮E治疗显著降低了小鼠中的γ-OHPdG水平。 Xpa-/-小鼠的肝脏DNA，将这些小鼠的HCC发病率从对照组的100%降低至14%。的 LCCC联盟由乔治城隆巴迪综合癌症中心组成，总部设在 华盛顿，DC（LCCC-DC）和Hackensack Meridian Health的John Theurer癌症中心， 位于新泽西州哈肯萨克（LCCC-NJ）。因此，LCCC服务区由LCCC-DC定义， LCCC 0 NJ集水区。由Jeffrey Toretsky博士和Benjamin Tycko博士领导，该计划 有21名成员和23名准成员，来自LCCC联盟机构的13个部门。在 本年度，MO成员得到768万美元（730万美元LCCC-DC，385,226美元LCCC-NJ）的支持， 研究补助金资金（年度直接费用），其中230万美元（192万美元LCCC-DC，385，226美元LCCC-NJ）是 同行评审和125.1万美元（在LCCC-DC）由国家癌症研究所（NCI）资助。MO是家 四项多人研究赠款金214篇癌症相关出版物证明了生产力，其中23篇 影响因子≥ 8的期刊。癌症和项目相关的出版物包括23%的跨- 方案内22%，方案间和方案内11%，36% 与其他癌症中心合作。办事处成员与其他三个地方协调中心的成员合作 研究计划（乳腺癌计划[BC]，癌症预防和控制计划[CPC]， 实验治疗计划[ET]），并使用所有九个共享资源。支持进行综合 专题研究，MO拥有重要的新技术专长，包括有条件地重新编程 细胞（CRC）、Zevatars和BiaCore 4000。

ABSTRACT The Georgetown Lombardi Comprehensive Cancer Center (LCCC) Molecular Oncology Program (MO) brings together investigators whose mission is to identify and validate molecular pathways critical to the initiation, progression, maintenance and metastases of cancer. The overall goals of MO are to understand and develop biomarkers for the complex processes of cancer susceptibility, initiation and progression, plus identify novel targets and novel and repurposed anti-cancer agents that show promise because of reduced toxicity against normal cells. To accomplish this mission and goals, MO members perform research under two 2 aims: 1) Define and exploit unique genomic and epigenomic events that initiate and sustain cancer growth and 2) determine the biological mechanisms that underlie stem cell-like phenotypes, altered metabolism and the metastatic spread of cancer cells. A significant advances that reflects progress in Aim 1 by Yi found that Yap modulates the immunosuppressive environment in pancreatic ductal adenocarcinoma (PDAC). For Aim 2, Chung identified theaphenon E treatment significantly decreased γ-OHPdG levels in the liver DNA of Xpa-/- mice that reduced HCC incidence in these mice to 14% from 100% in the controls. The LCCC Consortium is comprised of Georgetown Lombardi Comprehensive Cancer Center, based in Washington, DC (LCCC-DC) and the John Theurer Cancer Center of Hackensack Meridian Health, based in Hackensack, NJ (LCCC-NJ). Accordingly, the LCCC catchment area is defined by the LCCC-DC and LCCC0NJ catchment areas. Led by Jeffrey Toretsky, MD and Benjamin Tycko, MD, PhD, the program has 21 members and 23 associate members from 13 departments across LCCC Consortium institutions. In the current year, MO members are supported by $7.68M ($7.3M LCCC-DC, $385,226 LCCC-NJ) in research grant funding (annual direct costs) of which $2.3M ($1.92M LCCC-DC, $385,226 LCCC-NJ) is peer reviewed and $1.251M (at LCCC-DC) is funded by the National Cancer Institute (NCI). MO is home to four multi-investigator grants. Productivity is demonstrated by 214 cancer-related publications, 23 of which were in journals with an impact factor ≥ 8. Cancer and program-related publications included 23% inter- programmatic, 22% intra-programmatic, 11% inter- and intra-programmatic and 36% that involved collaborations with another cancer center. MO members collaborate with members of the other three LCCC Research Programs (Breast Cancer Program [BC], Cancer Prevention and Control Program [CPC], and Experimental Therapeutics Program [ET]) and use all nine Shared Resources. To support integrated thematic research, MO houses significant novel technical expertise, including conditionally reprogrammed cells (CRCs), Zevatars, and a BiaCore 4000.