Identification of Molecular Targets in Triple-Negative Breast Cancer

抑制雌激素通路或靶向扩增Her2/Neu的分子靶向治疗在乳腺癌治疗中是有效的。肿瘤不表达雌激素受体（ER）、孕激素受体（PR）或扩增Her2/Neu的患者（占乳腺癌患者的20%）不能从有效的靶向治疗（即抗雌激素治疗和赫赛汀）中获益，只能通过化疗治疗。这些三阴性肿瘤往往表现出较差的预后特征，与肿瘤表达ER、PR和/或Her2/Neu扩增的患者相比，表达这些肿瘤的患者预后较差。在一项新的倡议中，我们正在使用RNAi技术在功能基因组方法中识别三阴性乳腺癌细胞中的治疗靶点激酶。我们已经确定了一系列激酶，当它们被下调时，会导致癌细胞死亡。正在进行的工作是进一步表征这些激酶。

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.