The organelles of cancer cells must adapt to oncogenic stress for tumors to initiate and progress, but there is little to no systems-level understanding of how such adaptations occur. The Systems Analysis of Stress-adapted Cancer Organelles (SASCO) Center at the University of Virginia is addressing this challenge by mechanistic modeling of organellar processes that iterates with quantitative experiments in disease-relevant cell cultures and primary tumors. The Center brings together investigators with primary and collaborative track records in cancer biology, systems biology, genetically engineered mouse models of cancer, and clinical practice.