Response of metastatic mouse invasive lobular carcinoma to mTOR inhibition is partly mediated by the adaptive immune system.

ABSTRACT: Effective treatment of invasive lobular carcinoma (ILC) of the breast is hampered by late detection, invasive growth, distant metastasis, and poor response to chemotherapy. Phosphoinositide 3-kinase (PI3K) signaling, one of the major druggable oncogenic signaling networks, is frequently activated in ILC. We investigated treatment response and resistance to AZD8055, an inhibitor of mammalian target of rapamycin (mTOR), in the K14-cre;Cdh1^Flox/Flox;Trp53^Flox/Flox (KEP) mouse model of metastatic ILC. Inhibition of mTOR signaling blocked the growth of primary KEP tumors as well as the progression of metastatic disease. However, primary tumors and distant metastases eventually acquired resistance after long-term AZD8055 treatment, despite continued effective suppres

SUBMITTER: Klarenbeek S 

PROVIDER: S-EPMC7028325 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature