RON signalling promotes therapeutic resistance in ESR1 mutant breast cancer.

ABSTRACT:

Background

Oestrogen Receptor 1 (ESR1) mutations are frequently acquired in oestrogen receptor (ER)-positive metastatic breast cancer (MBC) patients who were treated with aromatase inhibitors (AI) in the metastatic setting. Acquired ESR1 mutations are associated with poor prognosis and there is a lack of effective therapies that selectively target these cancers.

Methods

We performed a proteomic kinome analysis in ESR1 Y537S mutant cells to identify hyperactivated kinases in ESR1 mutant cells. We validated Recepteur d'Origine Nantais (RON) and PI3K hyperactivity through phospho-immunoblot analysis, organoid growth assays, and in an in vivo patient-derived xenograft (PDX) metastatic model.

Results

We demonstrated that RON was hyperactivated in ESR1 mutant models, and in

SUBMITTER: Dustin D 

PROVIDER: S-EPMC7782501 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature