Mechanisms of signaling and disease progression

Research Team:  H. Band, V. Band, Bulun, Chakravarti, Chatterton, Clevenger, Cryns, Dimri, Gao, Kiyokawa, Levenson, Lupu, Ouchi, Zhu

Hormones and growth factors mediate their actions in breast cancer through receptor-associated signal transduction networks resulting in specific patterns of gene expression. These signaling networks are not linear in nature, but are highly intertwined by intermediary cross-talk mechanisms. Signaling and its concomitant cross-talk in breast cancer have been directly linked to a number of salient phenomena in this disease, including tumor growth, metastasis, and hormone and chemotherapy resistance. Thus, these transduction pathways represent ideal targets for pharmacologic intervention. To that end, a variety of receptor-associated signaling pathways are under examination including those utilizing estrogens (Bulun, Chakravarti, Chatterton), prolactin (Clevenger), EGF/her2 family members (H. Band, V. Band), chaperones (Clevenger, Cryns, Lupu), kinases/small GTP-binding proteins (H. Band, V. Band, Clevenger, Cryns, Kiyokawa), and transcription factors (Bulun, Chakravarti, Clevenger). Several multi-disciplinary approaches including crystal and solution structural analysis, lentiviral siRNA delivery, nanoengineering, and small molecule drug screening are currently being utilized to dissect breast cancer signaling with the near-term goal of development of novel therapeutics.

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