Three-dimensional (3D) customized scaffolds are anticipated in providing new frontiers in cells manipulation and advanced therapy methods. Here we demonstrate the application of hybrid 3D porous scaffolds, representing networks of highly aligned self-assembled ceramic nano-fibers, for culturing four types of cancer cells. Ultra-high aspect ratio (~~107) of graphene augmented fibers of tailored nano-topology is shown as an alternative tool to substantially affect cancerous gene expression, eventually due to differences in local biomechanical features of the cell-matrix interactions. Here we report a clear selective up- and down-regulation of groups of markers for breast cancer (MDA-MB231), colorectal cancer (CaCO2), melanoma (WM239A) and neuroblastoma (Kelly) depending on only fibers orientation and morphology without application of any other stimulus. Changes in gene expression are also revealed for Mitomycin C treatment of MDA-MB231, making the scaffold a suitable platform for testing of anticancer agents. This allows an opportunity for selective »clean» guidance to deep understanding mechanisms of cancer cells progressive growth and tumor formation without possible side effects by manipulation with the specific markers.