In silico analysis of genetic alterations in breast cancer associated skin lesions to guide 3D flipwell co-culture system performance in screening immunomodulatory therapies.

Summary: Breast cancer associated inflammatory skin rash (BCIR) presents a unique challenge in therapeutic screening due to its distinct phenotypic and genetic differences. This study focuses on leveraging computational models to explore genetic modifications in the skin of patients with breast cancer-associated cutaneous lesions. We aim to identify <u>key genetic drivers</u> that influence the development and progression of the skin lesions. By using the Chan Zuckerberg CELL by GENE Discover Differential Expression database, we have identified several robustly co-expressed genes. Cytokeratin genes KRT7 (CK7), KRT5 (CK5), KRT19 (CK19), but not KRT20 (CK20) or KRT6 (CK6), were more differentially expressed together with ATP1A1, CD14, CD19, as well as macrophage associated genes CD86, STAT1, IL1B. By further analyzing specific genetic alterations in breast cancer associated lesions, we aim to enhance performance of the <u>3D Flipwell co-culture system</u> - a novel co-culture system designed to model gut microbiome, epithelial and immune cell crosstalk - in screening immunomodulatory therapeutics. This integrated approach promises to refine the screening process for immunomodulatory treatments and could lead to more targeted and effective therapies for managing breast cancer-associated cutaneous lesions. Maria A. Beamer¹, Saori Furuta² 1. University of Michigan, Ann Arbor, MI, United States. 2. Case Western Reserve University, Cleveland, OH, United States. Innate Immunity, Microbiology, and Microbiome