Cancer Genes and Pathways

项目总结/摘要 癌症基因和途径（CGP）计划的研究重点是定义必要的分子和 肿瘤发病机制和成功治疗的生物学机制。这一基本目标的主要目标是 科学计划是发现，表征和验证新的肿瘤改变（遗传，分子和 细胞途径），以推动转化癌症研究，这将导致改善癌症患者的结果。这 是通过三个重叠的研究目标，集中在1）结构和功能的研究， 促进肿瘤发生的遗传和细胞核改变，2）内在的细胞过程和途径， 驱动恶性转化和肿瘤进展，以及3）肿瘤外在因素，如免疫细胞 和环境致癌物，有助于癌症的发展和抑制。关键科学 上一个资助期的成就包括确定了RAD 52蛋白在受损DNA修复中的作用 和基因组稳定性，识别转移性基因签名和驱动神经内分泌的药物途径 肿瘤（NET）的发病机制，并破译的基本机制，外部机械力 影响肿瘤细胞代谢。CGP成员包括42个正式成员和9个准成员， 四所学院的十七个系。上一个年度直接与癌症相关的同行评审资金 预算年度为670万美元，其中120万美元来自NCI。CGP成员高度协作， 在过去的四年中，作者或合著了384篇癌症相关的同行评议出版物，其中22%（n= 100） 85)方案内出版物占30%（n= 117），方案间出版物占54%（n= 206）。57 论文发表在高影响力期刊上（影响因子>10）。方案内/方案间和 多机构小组正在领导反映CGP研究广度的调查，包括 DNA修复和基因组不稳定性机制的进展，血液中的遗传和分子事件 细胞转化，动物肿瘤模型开发，肉瘤中的药物途径，新靶点和 NET的治疗，乳腺癌干细胞和转移中的G蛋白信号传导，免疫细胞活化和 肿瘤微环境，爱荷华州环境毒素的致癌作用， 黑素瘤在CCSG的背景下，CGP是指导和驱动的基础科学基础 通过与其他霍尔顿综合癌症中心（HCCC）的合作， 程序. CGP成员指导肿瘤采购，CGP提供积分， 为涉及所有四个HCCC同事的临床研究提供基因组学、免疫学和生物信息学支持 计划，大量跨计划出版物，以及CGP的关键领导作用 一个U 01和两个NCI SPORE赠款的成员。

PROJECT SUMMARY/ABSTRACT Research in the Cancer Genes and Pathways (CGP) program focuses on defining essential molecular and biological mechanisms underlying tumor pathogenesis and successful therapy. The primary goal of this basic science program is to discover, characterize, and validate new tumor alterations (genetic, molecular and cellular pathways) to fuel translational cancer research that will lead to improved cancer patient outcomes. This is accomplished through three overlapping research aims centered on the study of 1) structural and functional genetic and nuclear alterations that promote tumorigenesis, 2) intrinsic cellular processes and pathways that drive malignant transformation and tumor progression, and 3) tumor extrinsic factors, such as immune cells and environmental carcinogens, that contribute to cancer development and suppression. Key scientific achievements over the prior funding period include defining the role of RAD52 protein in damaged DNA repair and genome stability, identifying metastatic gene signatures and druggable pathways driving neuroendocrine tumor (NET) pathogenesis, and deciphering fundamental mechanisms by which external mechanical forces influence tumor cell metabolism. CGP membership includes 42 full and nine associate members spanning seventeen departments across four colleges. Annual direct cancer-relevant peer-reviewed funding in the last budget year was $6.7 million with $1.2 million from the NCI. CGP members are highly collaborative, having authored or co-authored 384 cancer-related peer-reviewed publications in the past four years, with 22% (n= 85) intraprogrammatic, 30% (n= 117) interprogrammatic, and 54% (n= 206) inter-institutional publications. 57 manuscripts appeared in high impact journals (Impact Factor >10). Productive intra/interprogrammatic and multi-institutional groups are leading investigations that reflect the breadth of CGP research, including advances in mechanisms of DNA repair and genome instability, genetic and molecular events underlying blood cell transformation, animal tumor model development, druggable pathways in sarcoma, novel targets and therapies for NETs, G-protein signaling in breast cancer stemness and metastasis, immune cell activation and the tumor microenvironment, carcinogenic effects of Iowa environmental toxins, and drug resistance in melanoma. In the context of the CCSG, CGP is the basic science foundation that is guided by and drives translational oncology through its partnership with other Holden Comprehensive Cancer Center (HCCC) programs. This is exemplified by CGP member direction of tumor procurement, CGP provision of integral genomic, immunological, and bioinformatics support for clinical studies involving colleagues in all four HCCC programs, the outstanding number of interprogrammatic publications, and key leadership roles of CGP members on a U01 and two NCI SPORE grants.