Hydroxychloroquine inhibits autophagy to potentiate antiestrogen responsiveness in ER+ breast cancer.

ABSTRACT:

Purpose

Estrogen receptor-α (ERα)-targeted therapies including tamoxifen (TAM) or Faslodex (ICI) are used to treat ER(+) breast cancers. Up to 50% of tumors will acquire resistance to these interventions. Autophagy has been implicated as a major driver of antiestrogen resistance. We have explored the ability of hydroxychloroquine (HCQ), which inhibits autophagy, to affect antiestrogen responsiveness.

Experimental design

TAM-resistant MCF7-RR and ICI-resistant/TAM cross-resistant LCC9 ER(+) breast cancer cells were injected into mammary fat pads of female athymic mice and treated with TAM and/or ICI in combination with oral low-dose HCQ.

Results

We show that HCQ can increase antiestrogen responsiveness in MCF7-RR and LCC9 cells and tumors, likely through the inhibition

SUBMITTER: Cook KL 

PROVIDER: S-EPMC4073207 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature