Cancer Biology Program (CBP)

癌症生物学计划：摘要 亚利桑那癌症大学癌症生物学项目(CBP)的首要科学目标 该中心(UACC)旨在了解癌症病因和进展背后的基本生物学过程。 我们的目标是利用我们在这些过程中产生的知识来确定新的治疗靶点和 生物标记物，并建立项目间的合作，将它们带到临床。的具体目标 CBP的任务是：(1)阐明控制肿瘤相关细胞生长和增殖的基本机制；(2) 确定癌症发生和发展的病因学机制；以及(3)确定肿瘤如何 微环境影响肿瘤的进展、侵袭和转移。CBP由16个国家中的52个成员组成 系和五所学院。CBP成员对基本癌症机制产生了重大影响，如 证明是第一个：(1)识别休眠细胞中的静止开关；(2)找到 肾癌中的富马酸水合酶和铁下垂；(3)中心体丢失是肾癌的主要驱动因素 前列腺癌的发生；(4)破译癌症特异性POLβ突变的潜在功能缺陷；(5) 确定TDP-43在DNA修复和应激颗粒中的作用；(6)确定雄激素受体之间的联系 (AR)和整合素α6β1在转移的去势抵抗前列腺癌中的作用；(7)发现雌激素受体在 抑制乳腺癌的机械侵袭；以及(8)破译幽门螺杆菌如何逃避 免疫系统启动胃癌。通过方案间协作和向 临床和转化性肿瘤学项目，CBP成员正在通过设计新的 针对前列腺癌和结肠癌的雄激素受体和糖原合成酶激酶的药物， 分别在肾癌中测试新的Fe+螯合剂；设计针对EGFR和 整合素miR6αβ1在乳腺癌和前列腺癌中的表达；评价miR130b作为一种新的胃癌生物标志物 癌症；使用有机/免疫细胞共培养为胰腺设计个性化的联合疗法 以及测试大麻素受体激动剂以克服乳腺癌患者的骨痛。UAccess 通过资助试点奖项和协调方案会议向CBP提供支持， 研讨会、务虚会和讲习班，以促进方案内和方案间的协作和跨学科 翻译研究。这些会议支持自2016年以来战略性招聘17名新教师。CBP有 同行评审资金基数为980万美元(直接成本)，其中200万美元(20%)来自国家癌症研究所， 720万美元(73%)来自其他国家卫生研究院，60万美元(6%)来自其他同行审查 消息来源。这意味着同行审查的资金比上一个项目期增加了49%。在.期间 在本项目期间，成员撰写了386份与癌症有关的出版物，其中46份(12%)是 方案内，78个(20%)是方案间的，187个(48%)是机构间的。此外，CBP 成员提交了29项专利，其中两项已获颁发，并指导了50多名学员。

CANCER BIOLOGY PROGRAM: ABSTRACT The overarching scientific goal of the Cancer Biology Program (CBP) at the University of Arizona Cancer Center (UACC) is to understand the basic biological processes that underlie cancer etiology and progression. Our goal is to use the knowledge we generate on these processes to identify new therapeutic targets and biomarkers and to establish interprogrammatic collaborations to bring them to the clinic. The Specific Aims of CBP are to: (1) elucidate the basic mechanisms that control tumor-relevant cell growth and proliferation; (2) identify etiologic mechanisms in cancer initiation and progression; and (3) determine how the tumor microenvironment influences progression, invasion, and metastasis. CBP is comprised of 52 Members in 16 departments and five colleges. CBP Members have made a significant impact on basic cancer mechanisms as evidenced by being the first to: (1) identify a quiescence switch in dormant cells; (2) find a link between fumarate hydratase and ferroptosis in kidney cancer; (3) demonstrate centrosome loss as a major driver of prostate cancer initiation; (4) decipher the underlying functional defects in cancer-specific Polβ mutations; (5) identify a role for TDP-43 in DNA repair and stress granules; (6) identify a link between the androgen receptor (AR) and integrin α6β1 in metastatic castration-resistant prostate cancer; (7) find a role for estrogen receptor in suppressing mechanical-driven invasion in breast cancer; and (8) decipher how Helicobacter pylori evades the immune system to initiate gastric cancer. Through interprogrammatic collaborations and hand-offs to the Clinical & Translational Oncology Program, CBP Members are translating their findings by designing new drugs to target the androgen receptor and glycogen synthetase kinase in prostate and colon cancer, respectively; testing new Fe+ chelating agents in kidney cancer; designing peptides to target EGFR and integrin α6β1 in breast and prostate cancer, respectively; evaluating miR130b as a new biomarker for gastric cancer; using organoid/immune cell co-cultures to design personalized combination therapies for pancreatic cancer; and testing cannabinoid receptor agonists to overcome bone pain in breast cancer patients. UACC provided support to CBP through funding of pilot awards and coordination of programmatic meetings, seminars, retreats, and workshops that foster intra- and interprogrammatic collaborations and transdisciplinary translational research. These meetings supported strategic recruitment of 17 new faculty since 2016. CBP has a peer-review funding base of $9.8M (direct costs) of which $2M (20%) is from the National Cancer Institute, $7.2M (73%) from other National Institutes of Health sources, and $0.6M (6%) from other peer-reviewed sources. This represents a 49% increase in peer-reviewed funding over the previous project period. During the current project period, Members authored 386 cancer-relevant publications, of which 46 (12%) were intraprogrammatic, 78 (20%) were interprogrammatic, and 187 (48%) were inter-institutional. In addition, CBP Members filed 29 patents, of which two were issued, and mentored over 50 trainees.