Abstract B60: Nanoparticles directed to IL13RA2 for targeted therapy of basal-like breast cancer

Basal-like breast cancer (BLBC) is among the most aggressive forms of breast cancer and is highly prevalent in young African-American women. It is nonresponsive to targeted hormonal therapy due to the lack of estrogen receptor, progesterone receptor, and HER2 expression. To identify effective targetable biomarkers for BLBC, we performed gene expression profiling of a breast cancer progression model system representing the different stages of the cancer. We discovered in metastatic BLBC cells high expression of IL13RA2, a cell surface receptor, which corresponded to poor survival in patients with high-grade tumors based on in silico meta-analysis of publicly available microarray datasets. To assess its functional roles in breast cancer progression, we knocked down IL13RA2 in BLBC cells and found that it is essential for lung colonization and tumorigenesis in vivo. Next, to establish the clinical utility of this candidate biomarker to inform prognosis, we performed immunohistochemical analysis of breast cancer tissue microarrays and found that IL13RA2 is overexpressed in a subset of lymph node metastases, hence supporting its role as a metastasis promoter. Based on these observations, we hypothesize that IL13RA2 may serve as a biomarker for disease stage and an active target for nanoparticle-mediated delivery of therapeutic agents to eradicate metastatic BLBC cells. We are in the process of conjugating gold nanoparticles with monoclonal antibodies to assess their binding specificity to IL13RA2-overexpressing cells in vitro and in vivo. Ultimately, these nanoparticles could be used to monitor disease spread as well as to actively target metastatic BLBC cells overexpressing IL13RA2 to block metastasis.

Citation Format: Chen Khuan Wong, Sandy Zhang, Bjorn Reinhard, Sam Thiagalingam. Nanoparticles directed to IL13RA2 for targeted therapy of basal-like breast cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B60.