Cancer Biology Program (CBP)

癌症生物学文摘：摘要 亚利桑那大学癌症中心癌症生物学项目（CBP）的首要科学目标 中心（UACC）的目的是了解癌症病因和进展的基本生物学过程。 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， 生物标志物，并建立跨计划的合作，把他们带到临床。的具体目标 CBP的目的是：（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）确定肿瘤是如何 微环境影响进展、侵袭和转移。CBP由16个成员国中的52个成员国组成。 学院和五所大学。CBP成员对基本的癌症机制产生了重大影响， 证明是第一个：（1）确定休眠细胞中的静止开关;（2）找到之间的联系 富马酸水合酶和铁凋亡在肾癌中的作用;（3）证明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突变中的潜在功能缺陷;（5） 确定TDP-43在DNA修复和应激颗粒中的作用;（6）确定雄激素受体与 (AR)和整合素α6β1在转移性去势抵抗性前列腺癌中的作用;（7）发现雌激素受体在 抑制乳腺癌中机械驱动的侵袭;和（8）破译幽门螺杆菌如何逃避 免疫系统启动胃癌。通过方案间协作和移交给 临床和转化肿瘤学计划，CBP成员正在通过设计新的 靶向前列腺癌和结肠癌中的雄激素受体和糖原合成酶激酶的药物， 在肾癌中测试新的Fe+螯合剂;设计靶向EGFR的肽， 整合素α6β1分别在乳腺癌和前列腺癌中;评估miR 130 b作为胃癌的新生物标志物 癌症;使用类器官/免疫细胞共培养物设计胰腺癌的个性化组合疗法 癌症;以及测试大麻素受体激动剂以克服乳腺癌患者的骨痛。UACC 通过资助试点奖励和协调方案会议，向海关及边境保护局提供支助， 研讨会，务虚会和讲习班，促进内部和跨方案的合作和跨学科 翻译研究自2016年以来，这些会议支持了17名新教师的战略招聘。CBP已 980万美元（直接成本）的同行评审资金基础，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%）来自其他同行评审 源这意味着同行评审资金比上一个项目期间增加了49%。期间 在本项目期间，成员撰写了386篇癌症相关出版物，其中46篇（12%）是 方案内的有78项（20%），方案间的有187项（48%）。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.