Cancer Biology

癌症生物学研究：总结 癌症生物学（CB）计划在霍林斯癌症中心（HCC）旨在发现遗传和表观， 人类癌症的遗传基础，揭示了癌症发生和发展的潜在机制， 通过全州范围内的治疗干预和预防机会， 是的。三大主题贯穿整个计划：1）癌症基因组学和遗传学; 2）分子调控， 基因表达;和3）肿瘤微环境和宏观环境。在所有领域都取得了重大进展。这 包括鉴定驱动乳腺癌细胞增殖的新型基质成纤维细胞特征; hnRNP E1及其靶向非编码RNA在头颈癌、乳腺癌和前列腺癌中的发现; PLEKHA 7作为一个关键的粘附连接组件，将RISC连接到连接处并调节RNA肿瘤， 基因表达;以及第一份鉴定WNT信号传导阻遏物的报告，裸角质层同源物1（NKD 1）， 作为指定肝细胞命运的FGF 2 R调节因子。基础性的发现正被转化为 诊所例如，前列腺中晚期糖基化终产物（AGE）富集的鉴定可以- cer患者发展为2期临床试验，旨在减少乳腺癌中的AGEs 和前列腺癌患者在一个服务不足的社区，其中大多数患者是贫困的社会经济 非裔美国人背景因此，本研究中的发现正在被应用于了解社会 癌症差异的经济和环境来源，并制定与以下方面相关的有针对性的干预措施： 集水区。该计划由菲利普领导，共有来自两所学院11个部门的30名成员 Howe博士是TGF β 1领域的领导者。CB促进内部，跨学科和跨学科的研究， 这些活动为大型合作项目和有影响力的科学发现提供了校外资金。 CB的直接资金总额为480万美元（不包括职业发展和培训赠款）， 自上次更新以来增加了60%，有14个NCI项目（200万美元），11个癌症相关赠款来自其他NIH 研究所（190万美元）和四个DOD/VAMC赠款（90万美元）。CB拥有先进的强大的合作研究高- 由一个强大的投资组合资助的P型和U型奖项，和多PI R 01照亮。自上次审查以来，CB 成员撰写了122份出版物，其中65%是合作撰写的。该计划的特殊影响- 搜索的重点是重大发现，许多具有转化潜力，在顶级期刊上描述 包括Cancer Cell、Mol Cell、Cell Stem Cell、Cancer Discov、Genes Dev、Nat Genet、Nat Meth、Nat Cell Biol，Nat Commun，J Clin Oncol和J Clin Invest。随着新的HCC领导层，强大的教师招聘，德- 支持基于团队的跨计划研究和资助倡议，并加强翻译科学 CB计划致力于推进所有三个主题领域的科学发现。

CANCER BIOLOGY PROGRAM: SUMMARY The Cancer Biology (CB) Program at the Hollings Cancer Center (HCC) seeks to discover the genetic and epi- genetic basis of human cancer, expose the underlying mechanisms involved in cancer initiation and progression, and develop new therapeutic strategies through statewide opportunities for treatment intervention and preven- tion. Three major themes cut across the program: 1) cancer genomics and genetics; 2) molecular regulation of gene expression; and 3) tumor micro- and macro-environment. Significant progress was made in all areas. This includes the identification of a novel stromal fibroblast signature that drives breast cancer cell proliferation; the discovery of hnRNP E1 and its target non-coding RNAs in head and neck, breast and prostate cancer; uncover- ing PLEKHA7 as a critical adherens junction component that tethers RISC to junctions and regulates RNA onco- gene expression; and the first report to identify a repressor of WNT signaling, naked cuticle homolog 1 (NKD1), as an FGF2R regulated factor that specifies hepatic cell fate. Fundamental discoveries are being translated into the clinic. For example, the identification of Advanced Glycation Endproduct (AGE) enrichment in prostate can- cer patients was developed into a phase 2 clinical trial aiming to pharmacologically reduce AGEs in breast and prostate cancer patients in an underserved community where most patients are of poor socioeconomic African American background. Thus, discoveries made in this study are being applied to understand the soci- oeconomic and environmental sources of cancer disparities and to develop tailored interventions relevant to the catchment area. The program, with 30 members from 11 departments in two colleges, is led by Philip Howe, PhD, a leader in the TGF field. CB fosters intra-, inter- and transdisciplinary research through initia- tives that have yielded extramural funding of large collaborative projects and impactful scientific discoveries. The total direct funding base for CB is $ 4.8 million (excluding career development and training grants), an increase of 60% since the prior renewal, with 14 NCI projects ($2M), 11 cancer-related grants from other NIH institutes ($1.9M), and four DOD/VAMC grants ($0.9M). CB has advanced strong collaborative research high- lighted by a strong portfolio of funded P- and U-type awards, and multi-PI R01s. Since the last review, CB members authored 122 publications, 65% of them collaborative. The exceptional impact of the program’s re- search is highlighted by significant discoveries, many with translational potential, described in top-tier journals including Cancer Cell, Mol Cell, Cell Stem Cell, Cancer Discov, Genes Dev, Nat Genet, Nat Meth, Nat Cell Biol, Nat Commun, J Clin Oncol, and J Clin Invest. With new HCC leadership, strong faculty recruitment, de- velopment of team-based interprogrammatic research and funding initiatives, and enhanced translational sci- ence infrastructure, the CB Program is poised to advance scientific discovery in all three thematic areas.