PP2A inhibition overcomes acquired resistance to HER2 targeted therapy.

ABSTRACT:

Background

HER2 targeted therapies including trastuzumab and more recently lapatinib have significantly improved the prognosis for HER2 positive breast cancer patients. However, resistance to these agents is a significant clinical problem. Although several mechanisms have been proposed for resistance to trastuzumab, the mechanisms of lapatinib resistance remain largely unknown. In this study we generated new models of acquired resistance to HER2 targeted therapy and investigated mechanisms of resistance using phospho-proteomic profiling.

Results

Long-term continuous exposure of SKBR3 cells to low dose lapatinib established a cell line, SKBR3-L, which is resistant to both lapatinib and trastuzumab. Phospho-proteomic profiling and immunoblotting revealed significant alteration

SUBMITTER: McDermott MS 

PROVIDER: S-EPMC4230643 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature