Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer.

ABSTRACT:

Background

Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER⁺) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility.

Methods

A panel of ER⁺ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1 ^wt</

SUBMITTER: Ribas R 

PROVIDER: S-EPMC5992820 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature