Identification of Molecular Targets in Triple-Negative Breast Cancer

三阴性乳腺癌分子靶标的鉴定

• 批准号: 7733384
• 负责人: Stanley Lipkowitz
• 金额: $ 18.57万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7733384
• 关键词: Breast Cancer Cell; Breast Cancer Treatment; Cancer Patient; Cessation of life; Estrogen Antagonists; Estrogen Receptors; Estrogen Therapy; Estrogens; Genes; Hormone Receptor; Knock-out; Lead; Molecular Target; Outcome; Pathway interactions; Patients; Phosphotransferases; Progesterone Receptors; RNA Interference; Roche brand of trastuzumab; Technology; Work; cancer cell; chemotherapy; functional genomics; malignant breast neoplasm; novel; prognostic; receptor; therapeutic target; tumor

Molecularly targeted therapies that inhibit the estrogen pathway or that target amplified Her2/Neu are efficacious in the treatment of breast cancer. Patients whose tumors do not express estrogen receptor (ER), progesterone receptor (PR), or amplified Her2/Neu, a subset comprising 20% of breast cancer patients, do not benefit from the validated targeted therapies (i.e., anti-estrogen therapies and Herceptin) and can only be treated with chemotherapy. These triple-negative tumors tend to present with poor prognostic features and the patients who express these tumors have a poor outcome compared to those whose tumors express ER, PR, and/or have amplified Her2/Neu. In a new initiative, we are using RNAi technology in a functional genomic approach to identify kinases that are therapeutic targets in triple-negative breast cancer cells. We have identified a list of kinases that, when downregulated, lead to death in the cancer cells. Ongoing work is characterizing these kinases further.

抑制雌激素途径或靶向扩增的 Her2/Neu 的分子靶向疗法可有效治疗乳腺癌。肿瘤不表达雌激素受体 (ER)、孕激素受体 (PR) 或扩增的 Her2/Neu 的患者（占乳腺癌患者的 20%）无法从经过验证的靶向治疗（即抗雌激素疗法和赫赛汀）中受益，只能接受化疗。这些三阴性肿瘤往往表现出较差的预后特征，并且与肿瘤表达 ER、PR 和/或扩增 Her2/Neu 的患者相比，表达这些肿瘤的患者预后较差。在一项新举措中，我们正在功能基因组方法中使用 RNAi 技术来识别作为三阴性乳腺癌细胞治疗靶点的激酶。我们已经确定了一系列激酶，当下调时，这些激酶会导致癌细胞死亡。正在进行的工作正在进一步表征这些激酶。