Scalability of the Mechanobiological Vulnerability Index (MVI) in Triple- Negative Breast Cancer: A Microgravity-Induced Platform for In Silico Target Discovery

Triple-negative breast cancer remains one of modern oncology’s most critical challenges, characterized by the absence of hormone receptors and HER2 overexpression—a profile that drastically restricts targeted therapeutic options and is associated with high aggressiveness, increased metastatic risk, and unfavorable prognosis. Despite advances in genomics-based precision oncology, limitations persist regarding approaches that consider only static molecular profiles without accounting for the fundamental physical and mechanical properties of tumor cells. Here, we propose the Mechanobiological Vulnerability Index (MVI), a scalable computational platform conceived on mechanobiological principles to investigate the hypothesis that simulated microgravity conditions induce profound structural alterations in the cytoskeleton and cell adhesion complexes—a disorganization capable of exposing neoantigens and cryptic epitopes normally masked under terrestrial gravity. The methodological strategy integrates experimental models of gravitational simulation with advanced deep learning architectures: U-Net networks for segmentation and structural analysis, and Vision Transformers (ViT) to capture complex patterns of morphological deformation. The MVI calculation formula is theoretically established as a quantitative metric that synthesizes deformation magnitude, degree of structural disorganization, alterations in mechanical signaling pathways, and the level of exposure of biological targets. It is anticipated that this methodological framework, when implemented and validated in subsequent stages, will exhibit a high degree of transferability to different tumor types, constituting an innovative complementary tool for the discovery of novel therapeutic targets and for deepening the understanding of the relationships between the physical properties of tumor cells and their response to treatments.