Understanding the Role of NIPBL loss on Drug Sensitivity in 3D Cancer Cell Line Cultures

Abstract

Breast cancer (BC) remains the most widespread cancer globally and stands as the fifth leading cause of mortality. Despite available therapeutic and preventive strategies for many BC subtypes, Triple-negative BC poses distinct challenges because of its high genomic instability and lack of conventional therapeutic biomarkers. This report offers a comprehensive overview of Triple-negative BC, emphasizing its unique attributes and genomic alterations. It further explores the present biomarkers aiding targeted therapies in Triple-negative BC, with a specific focus on the prospective role of NIPBL as a promising biomarker. The report subsequently presents the project’s scope, details its aims, objectives, methodologies, and materials used. More specifically, we find that loss of NIPBL in 3D cultures impacts vinka alkaloid sensitivity. Next, we investigated the expression of genes that encode known drug transporters and show that these are impacted by NIPBL loss and Vinorelbine treatment. In summary, we posit that NIPBL loss in cancer could represent as a negative prognostic biomarker for response to vinka alkaloids. 4