Defining Novel Targets for the Treatment of ER-negative Breast Cancers
Top Panel: Unsupervised hierarchical clustering of ER-negative breast tumors using kinases as well as kinase-associated genes. Middle Panel: Differential survival of patients with ER-positive and ER-negative breast cancer. Bottom Panel: Comparison of MAPK expression in ER-positive versus ER-negative breast cancer cell lines.
Our lab has discovered that kinase activation defines a number of clinically prognostic ER-negative patient subgroups. This study focuses on a specific kinase subset, the mitogen-activated protein kinase (MAPK) family of proteins. MAPKs are an essential group of molecules that transduce both extracellular and intracellular stimuli. These signals are passed to the nucleus where they regulate cell growth and cell death. Since MAPKs are critical for cellular development, malignant cells commonly exhibit alterations within this pathway that significantly increase their growth. We hypothesize that there is a set of MAPKs critical for the growth of ER-negative breast cancers. Using RNAi and small molecule inhibitors, we are investigating whether the targeting of these kinases affect biological characteristics including proliferation, apoptosis, migration, and invasion. We also utilize mouse models in order to understand the in vivo effects of kinase inhibition. By defining novel targets and using combinatorial strategies, we seek to uncover effective treatments for this deadly form of breast cancer.
- Speers C, Tsimelzon A, Sexton K, Herrick AM, Gutierrez C, Culhane A, Quackenbush J, Hilsenbeck S, Chang J and Brown P. Identification of novel kinase targets for the treatment of estrogen receptor-negative breast cancer. Clinical Cancer Research 15(20): 6327-40, 2009.
Lab members working on this research: