Exploring enzyme-instructed self-assembly (EISA) for targeting osteoblastic metastasis of prostate cancer

探索酶指导自组装(EISA)以靶向前列腺癌的成骨细胞转移

基本信息

  • 批准号:
    10044030
  • 负责人:
  • 金额:
    $ 43.05万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-01 至 2022-07-31
  • 项目状态:
    已结题

项目摘要

Abstract Prostate cancer (PCa) remains as the most frequent cancer and the second leading cause of cancer mortality among U.S. males that are mainly associated with metastatic diseases. Bone is the major site of distant metastases of PCa. Although androgen deprivation therapy (ADT) is effective for treating hormone naive PCa, the onset of metastatic castration-resistant prostate cancer (mCRPC) confers androgen resistant phenotypes, which is the end stage of disease without cure. Thus, developing novel approaches for treating mCRPC is urgently needed. It is well known the reciprocal interaction between PCa and bone microenvironment resulted in unique osteoblastic reaction that further promotes PCa progression. Thus, we hypothesize that dual targeting osteoblast and PCa cells should lead to a novel single agent as an effective targeted therapy for mCRPC. Therefore, we propose to explore enzyme-instructed self-assembly (EISA) for targeting osteoblastic mCRPC. The proposed research is to develop the EISA substrates that can undergo EISA by the actions of alkaline phosphatase (ALPL) and acid phosphatase (ACPP) and to examine their efficacy in cell assays. This research program will focus on three specific aims: Aim 1, design and synthesis of EISA substrates of ALPL and ACPP; Aim 2, characterizing the EISA substrates of ALPL and ACPP and determining their activities in the co- culture of osteoblast and mCRPC cells; and Aim 3, examining the efficacy of the EISA substrates for inhibiting mCRPC in clinically relevant animal models. The rigor of prior research is that (i) it is well documented that overexpression of ALPL is the feature of osteoblastic metastases and overexpression of ACPP is the feature of PCa and (ii) our preliminary results show that EISA catalyzed by ALPL selectively inhibits osteoblast model cells and EISA catalyzed by ACPP selectively inhibit CRPC cells. The success of the proposed studies will contribute to the development of new molecular targeting agents based on ALPL and ACPP overexpressed during the process of metastasis of mCRPC in bone, which may ultimately lead to breakthrough in treating mCRPC.
摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(2)

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Jer-Tsong Hsieh其他文献

Jer-Tsong Hsieh的其他文献

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{{ truncateString('Jer-Tsong Hsieh', 18)}}的其他基金

Targeting KDM4B, a novel alternative splicing regulator, in castration-resistant prostate cancer (CRPC)
靶向 KDM4B(一种新型选择性剪接调节因子)治疗去势抵抗性前列腺癌 (CRPC)
  • 批准号:
    10312132
  • 财政年份:
    2018
  • 资助金额:
    $ 43.05万
  • 项目类别:
Targeting KDM4B, a novel alternative splicing regulator, in castration-resistant prostate cancer (CRPC)
靶向 KDM4B(一种新型选择性剪接调节因子)治疗去势抵抗性前列腺癌 (CRPC)
  • 批准号:
    10116972
  • 财政年份:
    2018
  • 资助金额:
    $ 43.05万
  • 项目类别:
Developing targeted therapy with prostate cancer specific nanomedicine
开发前列腺癌特异性纳米药物的靶向治疗
  • 批准号:
    9325475
  • 财政年份:
    2013
  • 资助金额:
    $ 43.05万
  • 项目类别:
Developing targeted therapy with prostate cancer specific nanomedicine
开发前列腺癌特异性纳米药物的靶向治疗
  • 批准号:
    8615933
  • 财政年份:
    2013
  • 资助金额:
    $ 43.05万
  • 项目类别:
Targeting aggressive prostate cancer with novel theranostic nanomedicine
利用新型治疗诊断纳米药物治疗侵袭性前列腺癌
  • 批准号:
    8509520
  • 财政年份:
    2011
  • 资助金额:
    $ 43.05万
  • 项目类别:
Targeting aggressive prostate cancer with novel theranostic nanomedicine
利用新型治疗诊断纳米药物治疗侵袭性前列腺癌
  • 批准号:
    8336823
  • 财政年份:
    2011
  • 资助金额:
    $ 43.05万
  • 项目类别:
Targeting aggressive prostate cancer with novel theranostic nanomedicine
利用新型治疗诊断纳米药物治疗侵袭性前列腺癌
  • 批准号:
    8892816
  • 财政年份:
    2011
  • 资助金额:
    $ 43.05万
  • 项目类别:
Targeting aggressive prostate cancer with novel theranostic nanomedicine
利用新型治疗诊断纳米药物治疗侵袭性前列腺癌
  • 批准号:
    8703512
  • 财政年份:
    2011
  • 资助金额:
    $ 43.05万
  • 项目类别:
Targeting aggressive prostate cancer with novel theranostic nanomedicine
利用新型治疗诊断纳米药物治疗侵袭性前列腺癌
  • 批准号:
    8092399
  • 财政年份:
    2011
  • 资助金额:
    $ 43.05万
  • 项目类别:
The role of CAR and its application in bladder cancer
CAR的作用及其在膀胱癌中的应用
  • 批准号:
    7013967
  • 财政年份:
    2003
  • 资助金额:
    $ 43.05万
  • 项目类别:

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组织非特异性碱性磷酸酶在脑内皮细胞稳态中的作用
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