Targeting secreted factors in endocrine resistant breast cancer therapy

内分泌耐药乳腺癌治疗中的靶向分泌因子

基本信息

批准号：
10654343
负责人：
Kideok Jin
金额：
$ 48万
依托单位：
ALBANY COLLEGE OF PHARMACY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10654343
关键词：
Antibodies Antineoplastic Agents Aromatase Inhibitors Automobile Driving Binding Bioinformatics Biological Assay Biological Markers Breast Cancer Cell Breast Cancer Patient Breast Cancer cell line Breast Cancer therapy CCR5 gene CDK4 gene CRISPR/Cas technology Cell Communication Cell Line Cell Proliferation Cells Clinical Coculture Techniques Combined Modality Therapy Communication Conduct Clinical Trials Disease Drug Targeting Drug resistance ESR1 gene Endocrine Endoglin Estrogen Receptors Estrogen receptor positive Feedback Fibroblasts Fulvestrant Future Growth Invaded Investigation Knock-out Knowledge Ligand Binding Domain Lymphatic Endothelial Cells MAPK Signaling Pathway Pathway Macrophage Malignant Neoplasms Mammary Neoplasms Metastatic breast cancer Methods Migration Assay Molecular Target Mus Mutation Neoplasm Metastasis Organ Outcomes Research Patients Pharmaceutical Preparations Phenotype Play Point Mutation Postmenopause Protein Secretion RANTES Recurrence Regimen Resistance Resistance development Role Secondary to Signal Pathway Signal Transduction Solid Neoplasm Stromal Cells System Tamoxifen Testing Therapeutic Tissues Tube Up-Regulation Vascular Endothelial Cell Woman Xenograft procedure cancer clinical trial cell motility cell stroma cytokine design diagnostic biomarker dimethylbenzanthracene effective therapy experimental study genome editing hormone therapy inhibitor inhibitor therapy malignant breast neoplasm mouse model neoplastic cell new therapeutic target novel paracrine pre-clinical receptor screening therapeutic target transcription factor tumor tumor DNA tumor growth

项目摘要

Abstract/Summary: Various types of endocrine therapy have been used for postmenopausal women with early stage breast cancer. These therapies are safe and effective, but initially responsive breast tumors often develop resistance and eventually recur. Since a communication between tumor and tumor circumstance plays an important role to grow tumor and spread tumor to secondary organs, we examined the communication of endocrine resistant breast cancer with stroma which is the part of a tissue or organ that has a connective and structural role in cancer. We established four different endocrine resistant breast cancer cell lines and examined the communication of these cells with four stromal cells. We found that CCL5 and endoglin might play an important role in endocrine resistant breast cancer. Thus, we will 1) Investigate the role of CCL5 and endoglin in the crosstalk between ERBC cells and stromal cells, 2) Unveil the mechanism of the upregulated CCL5 and endoglin in crosstalk between ERBC and stroma, and 3) Develop therapeutic strategies to block the paracrine interaction between the stromal cell and ERBC cell. We will investigate which secreted factors could serve as a key regulator in the transition of breast cancer cells to endocrine resistance and gaining of an aggressive phenotype. Further, secreted factors from the communication between endocrine resistant breast cancer and stroma might prove to be an attractive target for breast cancer drugs. Most of the cancer drugs in use currently have been developed to directly impact tumor cells. These drugs do not do much to block signals coming from tumor circumstance. Our proposed investigation will give us a small list of the most potent of these signals. Drugs, some of which we will identify here, and others that will have to be developed, that block these signals could limit the ability of the tumors to spread to secondary organs, which should result in overall survival gains for patients.

摘要/总结：各种类型的内分泌治疗已用于治疗早期乳腺癌的绝经后妇女癌症。这些疗法安全有效，但最初有反应的乳腺肿瘤通常会产生耐药性并最终复发。由于肿瘤与肿瘤环境之间的通讯对于肿瘤的发生起着重要作用。生长肿瘤并将肿瘤扩散到次要器官，我们检查了内分泌抵抗的沟通具有间质的乳腺癌是具有结缔和结构作用的组织或器官的一部分癌症。我们建立了四种不同的内分泌抗性乳腺癌细胞系并检查了这些细胞与四个基质细胞的通讯。我们发现 CCL5 和内皮糖蛋白可能发挥重要作用在内分泌抵抗性乳腺癌中的作用。因此，我们将 1) 研究 CCL5 和内皮糖蛋白在 ERBC细胞与基质细胞之间的串扰，2）揭示CCL5和内皮糖蛋白上调的机制 ERBC 和基质之间的串扰，以及 3) 制定阻断旁分泌相互作用的治疗策略介于基质细胞和 ERBC 细胞之间。我们将研究哪些分泌因子可以作为乳腺癌转变的关键调节因子细胞产生内分泌抵抗并获得攻击性表型。此外，分泌因子内分泌抵抗性乳腺癌和间质之间的通讯可能被证明是一个有吸引力的目标乳腺癌药物。目前使用的大多数抗癌药物都是为了直接影响肿瘤而开发的细胞。这些药物对于阻断来自肿瘤环境的信号没有多大作用。我们提议的调查将为我们提供这些最有效信号的一小部分列表。毒品，其中一些我们将在这里识别，还有一些必须开发出阻断这些信号的药物，从而限制肿瘤扩散到继发性肿瘤的能力器官，这应该会导致患者总体生存率的提高。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Crosstalk between triple negative breast cancer and microenvironment.

三阴性乳腺癌与微环境之间的串扰。

DOI：
发表时间：
2023-03-31
期刊：
影响因子：
0
作者：
Smrekar, Karly;Belyakov, Artem;Jin, Kideok
通讯作者：
Jin, Kideok

The role of CXCL1 in crosstalk between endocrine resistant breast cancer and fibroblast.

CXCL1 在内分泌耐药乳腺癌和成纤维细胞之间的串扰中的作用。

DOI：
发表时间：
2024-02-23
期刊：
影响因子：
2.8
作者：
Pandithar, Sneha;Galke, Daniel;Akume, Ahone;Belyakov, Artem;Lomonaco, Dominick;Guerra, Amirah A;Park, Jay;Reff, Olivia;Jin, Kideok
通讯作者：
Jin, Kideok

Overview of the therapeutic strategies for ER positive breast cancer.

ER 阳性乳腺癌治疗策略概述。