Abstract LB_B17: Single-cell analysis of dynamic remodeling of radiated TNBC cells

Abstract The dynamic rearrangement of the cellular cytoskeletal network and changes in cellular stiffness play crucial roles in the progression of malignant tumors, including those with invasive and metastatic traits. Despite the acknowledged connections, the inherent complexity of cancer and the various microenvironments that individual cells experience during treatment have hindered comprehensive investigations into therapeutic responses, particularly at the individual cell level. Notably, the emergence of large DNA damage-induced cells following radiotherapy in the challenging-to-treat triple-negative breast cancer (TNBC) subtype suggests potential concurrent alterations in cellular mechanics. This study dives into the complex interplay among radiation therapy, cytoskeletal architecture, and cellular stiffness at the level of individual cells. By utilizing atomic force microscopy (AFM) as a quantitative and non-invasive technique, we discerned how cancer cells respond to radiation treatment based on their cytoskeletal properties. Our findings revealed a clear correlation between radiation therapy and disruptions in cytoskeletal integrity, along with a simultaneous increase in cellular stiffness. These observed changes could potentially indicate impending cell death or a reduced tendency for metastasis. Building on these insights, we propose that assessing cytoskeletal features through AFM holds potential for tailoring personalized radiation therapy approaches, depending on the distinct responses exhibited by cancer cells post-treatment. This shift in approach, guided by mechanics, underscores the capacity to enhance treatment effectiveness while minimizing unintended damage. By shedding light on the intricate interplay between radiation-induced cellular responses and mechanical properties, this study lays the foundation for innovative strategies that leverage cytoskeletal attributes to customize and optimize therapeutic interventions for TNBC and potentially other malignancies. Citation Format: Minhee Ku, Jin Sung Kim, Woong Sub Koom, Jaemoon Yang. Single-cell analysis of dynamic remodeling of radiated TNBC cells [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_B17.