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.
Public Health Relevance Statement: Public Health Relevance: Metastasis of aggressive breast cancer is a devastating and ultimately fatal condition. Currently there are no available treatment options which can effectively inhibit tumor invasion and metastasis. The goal of this proposal is to develop a non-toxic medication for the treatment and prevention of metastatic breast cancer.
Project Terms: Adverse effects; analog; base; BHLH Protein; Breast; Breast Cancer Cell; cancer cell; Cannabidiol; carcinogenesis; Cell Differentiation process; Cell Line; Cell Proliferation; Cells; Cessation of life; Chronic; clinical practice; Complement; cytotoxic; cytotoxicity; Data; design; Development; Disseminated Malignant Neoplasm; Down-Regulation; Drug Design; Drug Kinetics; Family; Future; Gene Expression; Goals; Growth; Helix-Turn-Helix Motifs; Housing; Human; in vivo; Inhibition of Cell Proliferation; inhibitor/antagonist; Lead; Legal patent; Libraries; malignant breast neoplasm; Malignant Neoplasms; Measures; Neoplasm Metastasis; neoplastic cell; Normal Cell; novel; novel therapeutic intervention; Outcome; Paclitaxel; Patients; Pharmaceutical Preparations; Phase; phase 2 study; Plants; Plasma Proteins; Pre-Clinical Model; Prevention; Property; Protein Binding; Proteins; public health relevance; Route; screening; Small Business Innovation Research Grant; Specificity; Staging; Stream; Therapeutic; Therapeutic Intervention; Tissues; Toxic effect; treatment strategy; Tumor Cell Invasion; tumor growth; Work
