Targeting activated PI3K/mTOR signaling overcomes acquired resistance to CDK4/6-based therapies in preclinical models of hormone receptor-positive breast cancer.

ABSTRACT:

Background

Combined targeting of CDK4/6 and ER is now the standard of care for patients with advanced ER+/HER2- breast cancer. However, acquired resistance to these therapies frequently leads to disease progression. As such, it is critical to identify the mechanisms by which resistance to CDK4/6-based therapies is acquired and also identify therapeutic strategies to overcome resistance.

Methods

In this study, we developed and characterized multiple in vitro and in vivo models of acquired resistance to CDK4/6-based therapies. Resistant models were screened by reverse phase protein array (RPPA) for cell signaling changes that are activated in resistance.

Results

We show that either a direct loss of Rb or loss of dependence on Rb signaling confers cross-resistance to inh

SUBMITTER: O'Brien NA 

PROVIDER: S-EPMC7427086 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature