Combined inhibition of Aurora A and p21-activated kinase 1 as a new treatment strategy in breast cancer

• DOI: 10.1007/s10549-019-05329-2
• Publication Date: 2019-06-28T07:11:22Z
• Authors: Vladislav Korobey...; Michelle Borakove; Yayi Feng; William M. Wuest; Alex B. Koval; Anna S. Nikonova; Ilya Serebriiskii; Jonathan Chernoff; Virginia F. Borges; Erica A. Golemis; Elena Shagisultanova
• Keywords: PAK1; Aurora inhibitor

The serine-threonine kinases Aurora A (AURKA) and p21-activated kinase 1 (PAK1) are frequently overexpressed in breast tumors, with overexpression promoting aggressive cancer phenotypes poor clinical outcomes. Besides the well-defined roles of these proteins control cell division, proliferation, invasion, both support MAPK pathway activation can contribute to endocrine resistance by phosphorylating estrogen receptor alpha (ERα). PAK1 directly phosphorylates AURKA its functional partners, suggesting potential value inhibiting activity tumors overexpressing and/or AURKA. Here, for first time, we evaluated effect combining inhibitor alisertib PAK FRAX1036 preclinical models cancer.Combination was a panel 13 human tumor lines BT474 xenograft model, assessment cycle FACS, signaling changes immunohistochemistry Western blot. Additionally, performed silico analysis identify markers response FRAX1036.Pharmacological inhibition synergistically decreased survival multiple lines, showing particular effectiveness luminal HER2-enriched models, inhibited growth ERα-driven model. In suggested dependence on most likely be sensitive inhibition.Dual targeting may promising therapeutic strategy treatment cancer, subtypes.