Phosphorylated ribosomal S6 (p-rpS6) as a post-treatment indicator of HER2 signalling targeted drug resistance

Abstract

Objective: To identify clinically relevant predictive biomarkers of trastuzumab resistance.

Material and methods: MTT, FACS assays, immunoblotting and immunocytochemistry were used to phenotypically characterize drug responses of two cell models BT474R and SKBR3R. Student's t-test and Spearman's correlation were applied for statistic analysis.

Results: The activity of a downstream effector of the HER2 pathway phosphorylated ribosomal protein S6 (p-rpS6), was suppressed by trastuzumab in the parental cell lines yet remained unchanged in the resistant cells following treatment. The level of p-rpS6 was inversely correlated to the drug induced growth inhibition of trastuzumab-resistant cells when they are treated with selected HER2 targeting drugs.

Conclusion: p-rpS6 is a robust post-treatment indicator of HER2 pathway-targeted therapy resistance.

• Biomarker
• breast cancer
• cell model
• drug response
• trastuzumab resistance

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

This work is supported by Norris Cancer Centre, Women's Cancer Program of the University of Southern California and was supported in part by award number P30CA015089 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Supplementary material available online

Supplementary Table S1 and Supplementary Figure S1-S4