Targeting breast cancer metastasis with inhibitors of Id-1

使用 Id-1 抑制剂靶向乳腺癌转移

• 批准号: 8516812
• 负责人: Anuradha Mahadevan
• 金额: $ 28.98万
• 依托单位: ORGANIX, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8516812
• 关键词: Adverse effects; BHLH Protein; Breast; Breast Cancer Cell; Cannabidiol; Cell Differentiation process; Cell Line; Cell Proliferation; Cells; Cessation of life; Chronic; Complement; Data; Development; Disseminated Malignant Neoplasm; Down-Regulation; Drug Design; Drug Kinetics; Family; Future; Gene Expression; Goals; Growth; Helix-Turn-Helix Motifs; Housing; Human; Inhibition of Cell Proliferation; Lead; Legal patent; Libraries; Malignant Neoplasms; Measures; Neoplasm Metastasis; Normal Cell; Outcome; Paclitaxel; Patients; Pharmaceutical Preparations; Phase; Plants; Plasma Proteins; Pre-Clinical Model; Prevention; Property; Protein Binding; Proteins; Route; Small Business Innovation Research Grant; Specificity; Staging; Stream; Therapeutic; Therapeutic Intervention; Tissues; Toxic effect; Tumor Cell Invasion; Work; analog; base; cancer cell; carcinogenesis; clinical practice; cytotoxic; cytotoxicity; design; in vivo; inhibitor/antagonist; malignant breast neoplasm; neoplastic cell; novel; novel therapeutic intervention; phase 2 study; public health relevance; screening; treatment strategy; tumor growth

DESCRIPTION (provided by applicant): Metastasis of aggressive breast cancer is a devastating and ultimately fatal condition. The current first- line agents which are used to treat breast cancer metastasis primarily target tumor growth. These drugs produce only modest increases in survival in patients with aggressive metastatic cancers and have significant side effects. Currently, there are no available treatment options that can specifically and effectively inhibit tumor invasion and metastasis. Therefore, novel drug strategies are needed to treat this chronic, fatal and incurable condition. Our therapeutic strategy for the treatment of aggressive breast cancer is based on reducing Id-1 expression. Id-1 is a key regulator of the invasive and metastatic potential of breast and additional cancers. In this Phase I proposal our focus will be on the optimization of our lead compound to discover one or more analogs that down-regulate Id-1 expression and consequently inhibit breast cancer cell invasion and metastasis. We will also optimize these compounds so that they display a favorable ADME-Tox profile. The ultimate goal of this proposal is to develop a novel therapeutic approach for the treatment of metastatic human breast cancers by down-regulation of Id-1.

描述（由申请人提供）：侵略性乳腺癌的转移是一种毁灭性的，最终是致命的状况。用于治疗乳腺癌转移的当前一线药物主要靶向肿瘤的生长。这些药物仅产生侵袭性转移性癌症患者的生存率较小，并具有明显的副作用。当前，没有可用的治疗选择可以具体有效地抑制肿瘤侵袭和转移。因此，需要新的药物策略来治疗这种慢性，致命和无法治愈的状况。我们治疗攻击性乳腺癌的治疗策略是基于降低ID-1表达的。 ID-1是乳房和其他癌症的侵入性和转移潜力的关键调节剂。在此阶段I建议中，我们的重点将放在铅化合物的优化上，以发现一种或多种下调ID-1表达并因此抑制乳腺癌细胞侵袭和转移的类似物。我们还将优化这些化合物，以便它们显示出良好的ADME-TOX配置文件。该提案的最终目标是开发一种新型的治疗方法，通过下调ID-1来治疗转移性人体乳腺癌。