Abstract P4-21-21: Her2 is not a cancer subtype but rather a driver found in all intrinsic subtypes and highly enriched in molecular apocrine tumors

The unfolded protein response (UPR) is an endoplasmic reticulum stress pathway controlled by the protein chaperone, glucose-regulated protein 78 (GRP78), to mediate inositol-requiring enzyme 1 (IRE1), PKR-like endoplasmic reticulum kinase (PERK), and activating transcription factor-6 (ATF6) signaling. UPR signaling has been shown to be upregulated in many different types of cancers, including breast cancer and melanoma, and is associated with the development of therapeutic resistance. These data suggest the importance of targeting UPR signaling as a possible cancer therapy. We have previously shown GRP78 to be upregulated in human breast tumor samples and leads to endocrine targeted therapy resistance. We recently showed inhibiting GRP78 in human orthotopic xenografts potentiates tamoxifen therapy effectiveness in sensitive tumors and restores endocrine therapy responsiveness in resistant tumors. In these GRP78-inhibited tumors there was a significant increase of CD68 positive macrophage population, suggesting that targeting UPR signaling has critical effects on the tumor microenvironment. Therefore, consideration of each UPR signaling component and how it effects the different cellular compartments of the tumor microenvironment need to be investigated to optimally induce both an antitumor immune effect and inhibit tumor epithelial cell growth. We now show deletion of GRP78, IRE1, and PERK through RNAi differentially regulates macrophage polarization. Specifically, PERK inhib...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Poster Session Abstracts Source Type: research