Mechanisms in Cancer Evolution Program

癌症演变机制计划（MCEP） 项目摘要 DLDCCC的癌症演变机制计划（MCEP）的使命集中在 理解产生异质性的分子机制（遗传和非遗传或表观遗传）， 环境驱动因素刺激癌症的演变。进化是通过变异发生的，变异创造了异质性 和选择。异源性是由内在的基因组和非遗传表型可塑性产生的 机制，以及通过外源性病毒、微生物组和营养物质改变细胞程序， 调变MCEP的目标是发现这些分子机制是如何 工作发现的新范例可以开辟新的翻译方向（贯穿DLDCCC计划和 其他人），包括新的进化生物标志物，诊断，预防和治疗工具。比如说， 尽管常规疗法杀死细胞或阻止它们生长（是抗增殖的），但提出了新的治疗方法。 干预措施将减缓进化，承诺新的和根本不同的方法来抑制肿瘤发生 并挫败抵抗此外，高度可进化细胞的生物标志物的鉴定可以允许检测处于风险中的细胞。 个体，以及癌症的早期检测。MCEP目前有26个成员：25个是研究成员 来自分子和人类遗传学，分子病毒学和微生物学， 生物化学和分子生物学，儿科肿瘤学，医学传染病，病理学和 免疫学，和赫芬顿老龄化中心;一个是兼职成员，在大学任命， 德克萨斯，奥斯汀。MCEP成员在上一次资助中共发表了576篇癌症相关论文 在影响因子为10或更高的期刊中，25%的期刊。在576份手稿中，11%代表了内部- 方案合作占46%，方案间合作占68%，机构间合作占68%。MCEP目前有一个 选定的与癌症有关的资金总额为1 050万美元（每年直接费用），其中包括200万美元， NCI，580万美元的其他NIH资金和220万美元的其他同行评审资金，主要来自癌症研究所。 德克萨斯州预防和研究倡议（CPRIT）。MCEP的两个目标包含以下机制 通过以下方式促进异质性：（1）内在进化启动子（突变，基因组重排， 重组、表观遗传的可遗传蛋白质和RNA错误介导的变异）;和（2）外部进化 启动子，包括病毒、一般微生物、微生物组和宿主和宿主的营养调节剂。 微生物组CCSG通过提供关键的共享资源，特别是高 参数流式细胞术;高级显微镜和图像信息学;基因组学，转录组学， 表观基因组学和单细胞，代谢组学和蛋白质组学;以及会议的行政支持， 俱乐部和兴趣小组，以及试点资金和招募资金。

Mechanisms in Cancer Evolution Program (MCEP) PROJECT SUMMARY The mission of the Mechanisms in Cancer Evolution Program (MCEP) at the DLDCCC is focused on understanding molecular mechanisms that generate heterogeneity (genetic and non-genetic or epi-genetic) and environmental drivers that spur evolution of cancers. Evolution occurs by variation, which creates heterogeneity and selection. Heterogeneity is generated by intrinsic genomic and non-genetic phenotype-plasticity mechanisms, as well as by alteration of cellular programs by extrinsic viruses, the microbiome, and nutritional modulation. The goal of the MCEP is fundamental basic science discovery of how these molecular mechanisms work. New paradigms discovered can open new translational directions (throughout the DLDCCC Programs and by others), including novel evolutionary biomarkers, diagnostic, preventative, and therapeutic tools. For example, whereas conventional therapies kill cells or stop them from growing (are anti-proliferative), proposed novel interventions that would slow evolution, promise new and fundamentally different ways to inhibit oncogenesis and thwart resistance. Also, identification of biomarkers of highly evolvable cells may allow detection of at-risk individuals, and earlier detection of cancers. The MCEP currently has 26 members: 25 are Research members from the BCM Departments of Molecular and Human Genetics, Molecular Virology and Microbiology, Biochemistry and Molecular Biology, Pediatrics-Oncology, Medicine-Infectious Disease, Pathology and Immunology, and the Huffington Center on Aging; one is an adjunct member, appointed at the University of Texas, Austin. Members of the MCEP published a total of 576 cancer-related papers in the previous funding period with 25% in journals with Impact Factors of 10 or above. Of the 576 manuscripts, 11% represented intra- programmatic, 46% inter-programmatic, and 68% inter-institutional collaborations. The MCEP currently has a total of $10.5 million in selected cancer-relevant funding (direct costs per annum), which includes $2 million from NCI, $5.8 million in other NIH funding and $2.2 million in other peer reviewed funding mostly from the Cancer Prevention and Research Initiative of Texas (CPRIT). The two MCEP Aims encompass mechanisms of promotion of heterogeneity by: (1) Intrinsic Evolution Promoters (mutation, genome rearrangement, recombination, epigenetic heritable protein- and RNA-error-mediated variation); and (2) Extrinsic Evolution Promoters, including viruses, microbes generally, the microbiome, and nutritional modulators of both host and microbiome. The CCSG supports this Research Program by providing key Shared Resources, particularly High- Parameter Flow Cytometry; Advanced Microscopy and Image Informatics; Genomic, Transcriptomic, Epigenomic and Single-Cell, Metabolomics, and Proteomics; as well as administrative support for meetings, clubs and interest groups, and pilot funding and recruitment funds.