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A combination of trastuzumab and BAG-1 inhibition synergistically targets HER2 positive breast cancer cells.
This study investigated the therapeutic potential of targeting the BAG-1 protein co-chaperone in trastuzumab-responsive or -resistant cells. In the METABRIC dataset, BAG-1 mRNA was significantly elevated in HER2+ breast tumors and predicted overall survival in a multivariate analysis (HR = 0.81; p = 0.022). In a breast cell line panel, BAG-1 protein was increased in HER2+ cells and was required for optimal growth as shown by siRNA knockdown. Overexpression of BAG-1S in HER2+ SKBR3 cells blocked growth inhibition by trastuzumab, whereas overexpression of a mutant BAG-1S protein (BAG-1S H3AB), defective in binding HSC70, pot...
Source: Oncotarget - March 10, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Abstract 737: Clonal evolution of the HER2 L755S mutation as a mechanism of acquired HER-targeted therapy resistance
Conclusion: Acquired L/LT resistance in the two BT474 R lines is due to selection of HER2 L755S subclones present in parental cells. The higher HER2 L755S levels in BT474 parentals compared with other parentals, and detection of its subclonal presence in a pre-treatment HER2+ BC patient, suggest that sensitive mutation detection methods will be needed to identify patients with potentially actionable HER family mutations in primary tumor. Treating this patient group with an irreversible TKI like Afa may prevent resistance and improve clinical outcome of this subset of HER2+ BC.Citation Format: Xiaowei Xu, Agostina Nardone, ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Xu, X., Nardone, A., Hu, H., Qin, L., Nanda, S., Heiser, L., Wang, N., Covington, K., Chen, E., Renwick, A., Mitchell, T., Shea, M., Wang, T., De Angelis, C., Contreras, A., Gutierrez, C., Fuqua, S., Chamness, G., Shaw, C., Li, M., Wheeler, D., Hilsenbeck Tags: Experimental and Molecular Therapeutics Source Type: research