Efficacy and PK/PD of a C/EBP beta antagonist in orthotopic breast cancer

C/EBP β 拮抗剂在原位乳腺癌中的疗效和 PK/PD

基本信息

  • 批准号:
    10681209
  • 负责人:
  • 金额:
    $ 80.35万
  • 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:
    2020-08-05 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Breast cancer (BC) remains an immense clinical challenge, particularly for late stage and metastatic disease. Prognosis for late-stage and metastatic disease is grim, with 5-year survival for Stage 4 metastatic disease at 22%, with a median survival of 3 years, resulting in approximately 40,000 deaths annually. As evident by these clinical outcomes, late stage and metastatic BC remains a high unmet medical need. Sapience’s ST101 provides a new opportunity to treat advanced or metastatic HER2-negative BC. The target of ST101 is C/EBPβ, which is a novel protein target active in cancer cells. C/EBPβ was previously considered an ‘undruggable’ target due to its (1) location inside of the nucleus of a cell and (2) activity dependent on protein-protein interactions, and not enzymatic activity. ST101 is a peptide antagonist of C/EBPβ interactions in tumor cells, resulting in transcriptional inhibition of survival factors, thereby triggering synthetic lethality and tumor apoptosis. Based on promising pre- clinical results, ST101 has moved into the clinical phase; it is currently in an open-label, two-part, phase 1/2 dose-finding study in patients with advanced, unresectable and metastatic solid tumors who have failed first- and second-line therapies. To further support the development of ST101 and improve its chances of clinical success, Sapience proposes to identify predictive and pharmacodynamic (PD) biomarkers for ST101 activity and demonstrate their utility in non-clinical patient-derived breast cancer (PDBC) models. Specific Aim #1 will identify predictive biomarkers of ST101 activity by screening a panel of PDBC models in 3-dimensional culture in vitro, and will identify genetic and/or C/EBPβ translational or post-translational modifications that correlate with ST101 sensitivity (or resistance). In Specific Aim #2, the identified biomarkers will be interrogated in in vivo patient- derived xenograft (PDX) mouse models, to assess whether they indeed predict ST101 success or failure. Finally, Specific Aim #3 proposes to identify PD biomarker(s) via differential gene expression (DGE) in tissue specimens used during Specific Aims #1 and #2, before and after ST101 exposure. In a clinical setting, these discoveries will be utilized for patient selection and tracking responses during treatment as an accompanying diagnostic/prognostic screen for ST101. The biomarkers would also be used to optimize dose or regimen.
摘要

项目成果

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Jim Rotolo其他文献

Jim Rotolo的其他文献

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{{ truncateString('Jim Rotolo', 18)}}的其他基金

Inhibition of SARS-CoV-2 infection with a pan-coronavirus anti-viral peptide
泛冠状病毒抗病毒肽抑制 SARS-CoV-2 感染
  • 批准号:
    10256216
  • 财政年份:
    2021
  • 资助金额:
    $ 80.35万
  • 项目类别:
Inhibition of SARS-CoV-2 infection with a pan-coronavirus anti-viral peptide
泛冠状病毒抗病毒肽抑制 SARS-CoV-2 感染
  • 批准号:
    10401492
  • 财政年份:
    2021
  • 资助金额:
    $ 80.35万
  • 项目类别:
Development of a cell-penetrating beta-catenin antagonist peptide as a therapeutic candidate for Wnt-driven breast cancer
开发细胞穿透性 β-连环蛋白拮抗剂肽作为 Wnt 驱动乳腺癌的候选治疗药物
  • 批准号:
    10707593
  • 财政年份:
    2021
  • 资助金额:
    $ 80.35万
  • 项目类别:
Development of a cell-penetrating beta-catenin antagonist peptide as a therapeutic candidate for Wnt-driven breast cancer
开发细胞穿透性 β-连环蛋白拮抗剂肽作为 Wnt 驱动乳腺癌的候选治疗药物
  • 批准号:
    10324076
  • 财政年份:
    2021
  • 资助金额:
    $ 80.35万
  • 项目类别:
Efficacy and PK/PD of a C/EBP beta antagonist in orthotopic breast cancer
C/EBP β 拮抗剂在原位乳腺癌中的疗效和 PK/PD
  • 批准号:
    10079655
  • 财政年份:
    2020
  • 资助金额:
    $ 80.35万
  • 项目类别:
Efficacy and PK/PD of a C/EBP beta antagonist in orthotopic breast cancer
C/EBP β 拮抗剂在原位乳腺癌中的疗效和 PK/PD
  • 批准号:
    10384382
  • 财政年份:
    2020
  • 资助金额:
    $ 80.35万
  • 项目类别:
Single-chain antibody countermeasures for the Radiation GI Syndrome
放射胃肠道综合症的单链抗体对策
  • 批准号:
    8646044
  • 财政年份:
    2014
  • 资助金额:
    $ 80.35万
  • 项目类别:
Single-chain antibody countermeasures for the Radiation GI Syndrome
放射胃肠道综合症的单链抗体对策
  • 批准号:
    8852053
  • 财政年份:
    2014
  • 资助金额:
    $ 80.35万
  • 项目类别:
Neutralization of ceramide as a novel approach to specifically inhibit acute GvHD
神经酰胺中和作为特异性抑制急性 GvHD 的新方法
  • 批准号:
    8514511
  • 财政年份:
    2012
  • 资助金额:
    $ 80.35万
  • 项目类别:
Neutralization of ceramide as a novel approach to specifically inhibit acute GvHD
神经酰胺中和作为特异性抑制急性 GvHD 的新方法
  • 批准号:
    8395366
  • 财政年份:
    2012
  • 资助金额:
    $ 80.35万
  • 项目类别:

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