Mays Cancer Center at UT Health SA

项目概要-癌症发展与进展（CDP）项目 癌症发展和进展（CDP）计划是三个高度互动的研究计划之一 Mays癌症中心（MCC）的研究人员在德克萨斯大学健康圣安东尼奥（UT Health SA）。帕特里克宋， D.Phil.和Ratna K. Vadlamudi博士是该计划的共同领导者。CDP计划的重点是 以实验室为基础的研究癌症病因学和进展的基本问题，也临床翻译 我们的研究发现。该计划有两个主题领域：1）基因组修复和表观遗传学和2）肿瘤 微环境。通过这些重点，CDP计划继续为实现 MCC的癌症预防和治疗目标，特别是对那些在我们大部分西班牙裔中不成比例的人， 南德克萨斯州的人口。该计划的具体目标是：1）追求基础和转化研究， 发现癌症特异性基因组改变，DNA修复机制和表观遗传编程， 有效地转化为临床; 2）发现机制并确定新的治疗靶点， 调节肿瘤转移、旁分泌信号传导、免疫信号传导和代谢。CDP计划 29名成员。他们代表了UT Health的Long医学院的八个不同的学术部门 一名成员来自德克萨斯大学奥斯汀分校。CDP计划成员持有1170万美元的同行- 审查了与癌症有关的资金（47笔赠款;直接费用）。NCI提供了170万美元的资金（通过12笔赠款）。 在上一个报告所述期间，CDP计划成员发表了260篇同行评审论文。其中， 26%是项目内合作的产品，21%是项目间合作的产品，77%是项目间合作的产品。 涉及多机构合作，包括84篇（42%）与其他NCI指定癌症相关的出版物 中心. CDP成员继续在他们的研究中广泛使用癌症中心支持的核心， 值得注意的是下一代测序，生物统计学和生物信息学，质谱，流式细胞术， 以及药物发现和结构生物学设施。CDP过去五年的科学成就 已经导致了几个范式转变的发现，高影响力的出版物（例如，自然，细胞，分子细胞， Nature Communications），开发用于定义癌症发展和进展的新模型 机制，转移性乳腺癌的抗体为基础的治疗，新的雌激素受体β激动剂 用于增强肿瘤抑制，以及用于治疗内分泌治疗耐药性的小分子抑制剂。CDP 成员-包括成功的新成员，他们的工作扩大了我们计划的重点-与 实验和发展治疗学（EDT）计划将研究转移到临床。多个赠款 已经在进行这些假设，其他假设正在审查中，并计划在即将提交的文件中提出。 在上一个报告期内，两项临床试验已开始转化CDP的发现：一项是在乳房中测试S-雌马酚 癌症（NCT 02352025），和一个测试丙咪嗪在三阴性乳腺癌（NCT 03122444）。

Project Summary-Cancer Development and Progression (CDP) Program The Cancer Development and Progression (CDP) Program is one of three highly interactive research programs of the Mays Cancer Center (MCC) at the University of Texas Health San Antonio (UT Health SA). Patrick Sung, D.Phil. and Ratna K. Vadlamudi, Ph.D. are Co-Leaders of the Program. The CDP Program focuses on laboratory-based studies of fundamental problems in cancer etiology and progression and also clinical translation of our research findings. The Program has two thematic areas: 1) Genomic Repair and Epigenetics and 2) Tumor Microenvironment. Through these foci, the CDP Program continues to make important contributions toward the MCC’s goal of cancer prevention and treatment, particularly for those disproportionate in our largely Hispanic population in South Texas. The Program’s Specific Aims are to: 1) Pursue basic and translational research to discover cancer-specific genome alterations, DNA repair mechanisms, and epigenetic programming that can be effectively translated to the clinic; and 2) Discover mechanisms and identify new therapeutic targets for modulating tumor metastases, paracrine signaling, immune signaling, and metabolism. The CDP Program has 29 members. They represent eight different academic departments in the Long School of Medicine at UT Health SA, and one member is from the University of Texas at Austin. CDP Program members hold $11.7M in peer- reviewed cancer-related funding (47 grants; direct costs). NCI provides $1.7M in funding (through 12 grants). Over the last reporting period, CDP Program members have published 260 peer-reviewed papers. Of these, 26% were products of intra-programmatic collaborations, 21% of inter-programmatic collaborations, and 77% involved multi-institutional collaborations, including 84 (42%) publications with other NCI-designated Cancer Centers. CDP members continue to use Cancer Center-supported cores extensively in their research, most notably, Next Generation Sequencing, Biostatistics and Bioinformatics, Mass Spectrometry, Flow Cytometry, and Drug Discovery and Structural Biology facilities. CDP scientific accomplishments over the past five years have resulted in several paradigm-shifting findings, high-impact publications (e.g. Nature, Cell, Molecular Cell, Nature Communications), development of novel models for defining cancer development and progression mechanisms, an antibody-based therapeutic for metastatic breast cancer, new estrogen receptor-beta agonists for enhancing tumor suppression, and small molecule inhibitors for treating endocrine therapy resistance. CDP members –including successful new recruits whose work expands our program’s focus – work closely with the Experimental and Developmental Therapeutics (EDT) Program to move research into the clinic. Multiple grants are already underway to pursue these hypotheses, with others in review and planned for upcoming submissions. In the last reporting period, two clinical trials have begun to translate CDP findings: one testing S-equol in breast cancer (NCT02352025), and one testing imipramine in triple-negative breast cancer (NCT03122444).